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1.
PLoS One ; 15(7): e0232507, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645007

RESUMO

Sex-related differences in cardiovascular diseases are highly complex in humans and model-dependent in experimental laboratory animals. The objective of this work was to comprehensively investigate key sex differences in the response to acute and prolonged adrenergic stimulation in C57Bl/6NCrl mice. Cardiac function was assessed by trans-thoracic echocardiography before and after acute adrenergic stimulation (a single sub-cutaneous dose of isoproterenol 10 mg/kg) in 15 weeks old male and female C57Bl/6NCrl mice. Thereafter, prolonged adrenergic stimulation was achieved by sub-cutaneous injections of isoproterenol 10 mg/kg/day for 14 days in male and female mice. Cardiac function and morphometry were assessed by trans-thoracic echocardiography on the 15th day. Thereafter, the mice were euthanized, and the hearts were collected. Histopathological analysis of myocardial tissue was performed after staining with hematoxylin & eosin, Masson's trichrome and MAC-2 antibody. Gene expression of remodeling and fibrotic markers was assessed by real-time PCR. Cardiac function and morphometry were also measured before and after isoproterenol 10 mg/kg/day for 14 days in groups of gonadectomized male and female mice and sham-operated controls. In the current work, there were no statistically significant differences in the positive inotropic and chronotropic effects of isoproterenol between male and female C57Bl/6NCrl. After prolonged adrenergic stimulation, there was similar degree of cardiac dysfunction, cardiac hypertrophy, and myocardial fibrosis in male and female mice. Similarly, prolonged isoproterenol administration induced hypertrophic and fibrotic genes in hearts of male and female mice to the same extent. Intriguingly, gonadectomy of male and female mice did not have a significant impact on isoproterenol-induced cardiac dysfunction as compared to sham-operated animals. The current work demonstrated lack of significant sex-related differences in isoproterenol-induced cardiac hypertrophy, dysfunction, and fibrosis in C57Bl/6NCrl mice. This study suggests that female sex may not be sufficient to protect the heart in this model of isoproterenol-induced cardiac dysfunction and underscores the notion that sexual dimorphism in cardiovascular diseases is highly model-dependent.


Assuntos
Cardiopatias/fisiopatologia , Caracteres Sexuais , Animais , Biomarcadores/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Modelos Animais de Doenças , Ecocardiografia , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/metabolismo , Cardiopatias/patologia , Isoproterenol/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia
2.
Life Sci ; 249: 117476, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32119962

RESUMO

Mangiferin is a well-known xanthone extracted from mango leaves (Mangifera indica Linn). Mangiferin is widely distributed in the bark, peel, leaf, seed, stalk, and kernel of mango and higher plants. The pharmacological properties of mangiferin, including its antioxidant, anticancer, antiaging, antiviral, hepatoprotective, analgesic, and immunomodulatory activities, have been described in several studies. We investigated the effect of mangiferin on isoproterenol-induced apoptosis. Experimental heart failure was induced in rats by intraperitoneal administration of isoproterenol (5 mg/kg) for 7 consecutive days. Rats were divided into five groups: group I (sham rats), group II (isoproterenol alone control), group III (isoproterenol + 25 mg/kg mangiferin), group IV (isoproterenol + 50 mg/kg mangiferin), and group V (isoproterenol + 0.0225 mg/kg digitalis as a positive control). Hemodynamic parameters and body weight, heart weight and liver weight, apoptosis induction, and caspase-3, Bax, and Bcl-2 protein levels were measured, and a histopathological analysis of cardiomyocytes was performed. In addition, apoptosis and protein expression of caspase-3, cleaved caspase-3, Bax, and Bcl-2 were measured in cardiac H9c2 cells. Mangiferin supplementation significantly increased heart rate and improved the maximum rate of decrease in left ventricular (LV) pressure, the maximum rate of increase in LV pressure, and LV systolic pressure. Mangiferin reduced inflammatory cell infiltration and the number of broken myocardial fibers, and decreased apoptosis in cardiomyocytes by reducing proteins levels of caspase-3 and Bax and increasing those of Bcl-2. Our findings suggest that mangiferin has a cardioprotective effect against isoproterenol-induced apoptosis in cardiomyocytes.


Assuntos
Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Insuficiência Cardíaca/induzido quimicamente , Coração/efeitos dos fármacos , Xantonas/farmacologia , Animais , Cardiotônicos/administração & dosagem , Injeções Intraperitoneais , Isoproterenol/administração & dosagem , Isoproterenol/farmacologia , Ratos
3.
Circ Heart Fail ; 13(3): e006331, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32164435

RESUMO

BACKGROUND: Chronotropic incompetence is common in heart failure with preserved ejection fraction (HFpEF) and is associated with impaired aerobic capacity. We investigated the integrity of cardiac ß-receptor responsiveness, an important mechanism involved in exertional increases in HR, in HFpEF and control subjects. METHODS: Thirteen carefully screened patients with HFpEF and 13 senior controls underwent exercise testing and graded isoproterenol infusion to quantify cardiac ß-receptor-mediated HR responses. To limit autonomic neural influences on heart rate (HR) during isoproterenol, dexmedetomidine and glycopyrrolate were given. Isoproterenol doses were increased incrementally until HR increased by 30 beats per minute. Plasma levels of isoproterenol at each increment were measured by liquid chromatography with electrochemical detection and plotted against HR. RESULTS: Peak VO2 and HR (117±15 versus 156±15 beats per minute; P<0.001) were lower in HFpEF than senior controls. Cardiac ß-receptor sensitivity was lower in HFpEF compared to controls (0.156±0.133 versus 0.254±0.166 beats per minute/[isoproterenol ng/mL]; P<0.001). Seven of 13 HFpEF subjects had ß-receptor sensitivity similar to senior controls but still had lower peak HRs (122±14 versus 156±15 beats per minute; P<0.001). CONCLUSIONS: Contrary to our hypothesis, patients with HFpEF displayed impaired cardiac ß-receptor sensitivity compared with senior controls. In the 7 out of 13 patients with HFpEF with age-appropriate ß-receptor sensitivity, peak HR remained low, suggesting impaired sinus node ß-receptor function may not fully account for low exercise HR response. Rather in some patients with HFpEF, chronotropic incompetence might reflect premature cessation of exercise before maximal sinus node activation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02524145.


Assuntos
Tolerância ao Exercício , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca , Receptores Adrenérgicos beta/metabolismo , Nó Sinoatrial/fisiopatologia , Volume Sistólico , Função Ventricular Esquerda , Adaptação Fisiológica , Agonistas Adrenérgicos beta/administração & dosagem , Idoso , Estudos de Casos e Controles , Teste de Esforço , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Humanos , Isoproterenol/administração & dosagem , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Receptores Adrenérgicos beta/efeitos dos fármacos , Nó Sinoatrial/efeitos dos fármacos , Nó Sinoatrial/metabolismo , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
4.
Physiol Rep ; 7(24): e14308, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31872972

RESUMO

Obesity is characterized by a blunted lipolytic response in abdominal subcutaneous adipose tissue (SAT) and low circulating vitamin D levels. Here we investigated whether an impaired SAT lipolytic response coincides with an impaired SAT vitamin D release in eight lean and six obese men. 25-hydroxyvitamin D3 [25(OH)D3 ] and 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] fluxes across SAT were measured using arterio-venous blood sampling in combination with AT blood flow measurements after an overnight fast and during 1-hr intravenous infusion of the non-selective ß-adrenergic agonist isoprenaline (20 ng·kg FFM-1 ·min-1 ). 1,25(OH)2 D3 was released across abdominal SAT during isoprenaline infusion in lean [-0.01 (-0.04 to 0.00) pmol*100 g tissue-1 *min-1 , p = .017 vs. zero flux], but not in obese men [0.01 (0.00 to 0.02) pmol*100 g tissue-1 *min-1 , p = .116 vs. zero flux], and accompanied by an impaired isoprenaline-induced lipolytic response in abdominal SAT of obese versus lean men. Isoprenaline had no significant effects on net 25(OH)D3 release across abdominal SAT and plasma vitamin D metabolites in lean and obese men. To conclude, a blunted isoprenaline-mediated lipolysis is accompanied by reduced release of 1,25(OH)2 D3 vitamin D across abdominal SAT in obesity.


Assuntos
Gordura Abdominal/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Di-Hidroxicolecalciferóis/metabolismo , Isoproterenol/farmacologia , Obesidade/metabolismo , Gordura Abdominal/efeitos dos fármacos , Agonistas Adrenérgicos beta/administração & dosagem , Adulto , Di-Hidroxicolecalciferóis/sangue , Humanos , Infusões Intravenosas , Isoproterenol/administração & dosagem , Lipólise , Masculino , Pessoa de Meia-Idade
5.
Am J Health Syst Pharm ; 76(8): 551-553, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-31420984

RESUMO

PURPOSE: A cost-reduction strategy for isoproterenol use in radiofrequency catheter ablation procedures was evaluated. SUMMARY: A medication-use evaluation at a 454-bed tertiary medical center revealed that the cardiac catheterization laboratory was the highest user of isoproterenol. Isoproterenol was removed from all AcuDose-Rx machines Omnicell, Mountain View, CA, and compounding was performed by pharmacy personnel. It was initially provided to the cardiac catheterization laboratory as an 8-µg/mL concentration in 20-mL 0.9% sodium chloride injection syringes with a 24-hour beyond-use date. This resulted in an initial cost savings but with an unacceptably high rate of wastage. Isoproterenol was then compounded as a 4-µg/mL concentration in 30 mL 5% dextrose in water syringes with a 9-day beyond-use date after a thorough literature search supported longer stability with this admixture. After 12 months of our current process, isoproterenol use during radio frequency catheter ablations (RFCAs) in the cardiac catheterization laboratory was reduced by 85%, decreasing the number of ampules used from 11.15 to 1.66 per week. CONCLUSION: A pharmacy-initiated process to mitigate an extraordinary increase in isoproterenol acquisition cost resulted in a reduction in usage in a tertiary care community hospital. Isoproterenol usage was reduced 85% after two different interventions were implemented, which is estimated to save $1,839 per procedure.


Assuntos
Ablação por Cateter/métodos , Redução de Custos , Composição de Medicamentos/métodos , Isoproterenol/economia , Serviço de Farmácia Hospitalar/economia , Ablação por Cateter/economia , Ablação por Cateter/instrumentação , Composição de Medicamentos/economia , Custos de Medicamentos/estatística & dados numéricos , Estabilidade de Medicamentos , Armazenamento de Medicamentos/economia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Custos Hospitalares/estatística & dados numéricos , Humanos , Isoproterenol/administração & dosagem , Estudos Retrospectivos , Centros de Atenção Terciária/economia , Centros de Atenção Terciária/estatística & dados numéricos , Fatores de Tempo
6.
Hypertension ; 74(2): 295-304, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31291149

RESUMO

Subendocardial damage is among the first cardiac manifestations of hypertension and is already present in asymptomatic disease states. Accordingly, markers of subendocardial impairment may facilitate early detection of cardiac damages and risk stratification under these conditions. This study aimed to investigate the impact of subendocardial damage on myocardial microstructure and function to elucidate early pathophysiologic processes and to identify corresponding diagnostic measures. Mice (n=38) were injected with isoproterenol to induce isolated subendocardial scarring or saline as corresponding control. Cardiac function and myocardial deformation were determined by high-frequency echocardiography. The cardiac stress response was assessed in a graded exercise test and during dobutamine stress echocardiography. Myocardial microstructure was studied ex vivo by 7 T diffusion tensor magnetic resonance imaging at a spatial resolution of 100×100×100 µm 3 . Results were correlated with histology and biomarker expression. Subendocardial fibrosis was accompanied by diastolic dysfunction, impaired longitudinal deformation (global peak longitudinal strain [LS]: -12.5±0.5% versus -15.6±0.5%; P<0.001) and elevated biomarker expression (ANP [atrial natriuretic peptide], Galectin-3, and ST2). Systolic function and cardiac stress response remained preserved. Diffusion tensor magnetic resonance imaging revealed a left-shift in helix angle towards lower values in isoproterenol-treated animals, which was mainly determined by subepicardial myofibers (mean helix angle: 2.2±0.8° versus 5.9±1.0°; P<0.01). Longitudinal strain and subepicardial helix angle were highly predictive for subendocardial fibrosis (sensitivity, 82%-92% and specificity, 89%-90%). The results indicate that circumscribed subendocardial damage alone can cause several hallmarks observed in cardiovascular high-risk patients. Microstructural remodeling under these conditions involves also remote regions, and corresponding changes in longitudinal strain and helix angle might serve as diagnostic markers.


Assuntos
Endocárdio/patologia , Interpretação de Imagem Assistida por Computador , Isoproterenol/efeitos adversos , Imagem Cinética por Ressonância Magnética/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Ecocardiografia/métodos , Endocárdio/diagnóstico por imagem , Endocárdio/lesões , Fibrose/diagnóstico por imagem , Fibrose/patologia , Alemanha , Humanos , Imuno-Histoquímica , Injeções Subcutâneas , Isoproterenol/administração & dosagem , Modelos Lineares , Camundongos , Camundongos Endogâmicos , Curva ROC , Distribuição Aleatória , Valores de Referência , Volume Sistólico/fisiologia , Análise de Sobrevida , Disfunção Ventricular Esquerda/patologia
7.
Int J Mol Sci ; 20(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071921

RESUMO

Activation of multiple pathways is associated with cardiac hypertrophy and heart failure. We previously published that CXCR4 negatively regulates ß-adrenergic receptor (ß-AR) signaling and ultimately limits ß-adrenergic diastolic (Ca2+) accumulation in cardiac myocytes. In isolated adult rat cardiac myocytes; CXCL12 treatment prevented isoproterenol-induced hypertrophy and interrupted the calcineurin/NFAT pathway. Moreover; cardiac specific CXCR4 knockout mice show significant hypertrophy and develop cardiac dysfunction in response to chronic catecholamine exposure in an isoproterenol-induced (ISO) heart failure model. We set this study to determine the structural and functional consequences of CXCR4 myocardial knockout in the absence of exogenous stress. Cardiac phenotype and function were examined using (1) gated cardiac magnetic resonance imaging (MRI); (2) terminal cardiac catheterization with in vivo hemodynamics; (3) histological analysis of left ventricular (LV) cardiomyocyte dimension; fibrosis; and; (4) transition electron microscopy at 2-; 6- and 12-months of age to determine the regulatory role of CXCR4 in cardiomyopathy. Cardiomyocyte specific-CXCR4 knockout (CXCR4 cKO) mice demonstrate a progressive cardiac dysfunction leading to cardiac failure by 12-months of age. Histological assessments of CXCR4 cKO at 6-months of age revealed significant tissue fibrosis in knockout mice versus wild-type. The expression of atrial naturietic factor (ANF); a marker of cardiac hypertrophy; was also increased with a subsequent increase in gross heart weights. Furthermore, there were derangements in both the number and the size of the mitochondria within CXCR4 cKO hearts. Moreover, CXCR4 cKO mice were more sensitive to catocholamines, their response to ß-AR agonist challenge via acute isoproterenol (ISO) infusion demonstrated a greater increase in ejection fraction, dp/dtmax, and contractility index. Interestingly, prior to ISO infusion, there were significant differences in baseline hemodynamics between the CXCR4 cKO compared to littermate controls. However, upon administering ISO, the CXCR4 cKO responded in a robust manner overcoming the baseline hemodynamic deficits reaching WT values supporting our previous data that CXCR4 negatively regulates ß-AR signaling. This further supports that, in the absence of the physiologic negative modulation, there is an overactivation of down-stream pathways, which contribute to the development and progression of contractile dysfunction. Our results demonstrated that CXCR4 plays a non-developmental role in regulating cardiac function and that CXCR4 cKO mice develop a progressive cardiomyopathy leading to clinical heart failure.


Assuntos
Cardiomiopatias/genética , Insuficiência Cardíaca/genética , Receptores CXCR4/genética , Animais , Fator Natriurético Atrial/genética , Cardiomiopatias/fisiopatologia , Quimiocina CXCL12/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Coração/efeitos dos fármacos , Coração/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Isoproterenol/administração & dosagem , Camundongos , Camundongos Knockout , Mitocôndrias Cardíacas/genética , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Receptores Adrenérgicos beta/genética , Transdução de Sinais/genética
8.
PLoS One ; 14(5): e0217030, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116771

RESUMO

Renin-angiotensin system (RAS) systemically or locally collaborates with tissue homeostasis, growth and development, which has been extensively studied for its pharmacological implications. This study was primarily aimed at finding and characterizing local RAS in rat parotid, sublingual and submandibular glands. It was also hypothesized that vasoactive drugs could affect the expression of RAS targets, as well as saliva flow and its composition. Therefore, another objective of this study was to compare the effects of losartan (angiotensin II receptor blocker) and isoproterenol (ß-adrenergic receptor agonist). Forty-one Wistar rats were divided into three groups and administered a daily intraperitoneal dose of saline, losartan or isoproterenol solutions for one week. The following RAS targets were studied using qPCR: renin (REN), angiotensinogen (AGT), angiotensin converting enzyme (ACE), ACE-2, elastase-2 (ELA-2), AT1-a and MAS receptors, using RPL-13 as a reference gene. Morphology of glands was analyzed by immunohistochemistry using REN, ACE, ACE-2, AT1, AT2 and MAS antibodies. The volume and total protein content of saliva were measured. Our results revealed that ACE, ACE-2, AT1-a, AT2 and MAS receptors were expressed in all salivary gland samples, but REN and ELA-2 were absent. Losartan decreased mRNA expression of RAS targets in parotid (MAS) and submandibular glands (ACE and both AT receptors), without affecting morphological alterations, and significantly decreased saliva and total protein secretions. Isoproterenol treatment affected gene expression profiles in parotid (ACE, ACE-2, AT1-a, MAS, AGT), and submandibular (ACE, AT2, AGT) glands, thus promoting acinar hypertrophy in serous acini, without significant changes in salivary flow or total protein content. These drugs affected mainly acini, followed by duct systems and myoepithelial cells, whereas blood vessels were not affected. In conclusion, there is a local RAS in major rat salivary glands and losartan, an angiotensin II receptor blocker, affected not only the RAS-target gene expression but also decreased salivary flow and total protein content.


Assuntos
Isoproterenol/administração & dosagem , Losartan/administração & dosagem , Sistema Renina-Angiotensina , Glândulas Salivares/efeitos dos fármacos , Agonistas Adrenérgicos beta/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Angiotensinogênio/metabolismo , Animais , Imuno-Histoquímica , Masculino , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Renina/metabolismo , Saliva/química , Serina Endopeptidases/metabolismo
9.
Acupunct Med ; 37(1): 55-63, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30843422

RESUMO

OBJECTIVES: To investigate the effect of acupuncture at PC6 on cardiac hypertrophy in isoproterenol (ISO)-treated mice. METHODS: 48 male C57BL/6 mice underwent subcutaneous injection of ISO for 14 days and were randomly divided into four groups (n=12 each) that remained untreated (ISO group), received verum manual acupuncture (MA) treatment at PC6 (ISO+MA(PC6) group), sham MA at location on the tail not corresponding to any traditional acupuncture point (ISO+MA(tail) group), or propranolol (ISO+PR group). An additional 12 mice were given an injection of phosphate-buffered saline (PBS) and formed a healthy control (Normal) group. After performing echocardiography and measuring the ratio of heart weight (HW)/tibia length (TL) at 14 days, all mice were euthanased. Morphological examination was performed following haematoxylin and eosin and Masson's staining of heart tissues. Ultrastructural changes were observed by electron microscopy. Cardiac protein expression of atrial natriuretic peptide (ANP) and tumour necrosis factor α (TNFα) were measured by immunohistochemical (IHC) staining and Western blotting. RESULTS: Compared with the untreated model group, acupuncture at PC6 lowered the heart rate, reduced the ratio of HW/TL, improved the left ventricular (LV) anterior wall thickness (LVAWd), LV end-diastolic anterior wall thickness (LVAWs), LV end-systolic posterior wall thickness (LVPWd), LV end-diastolic posterior wall thickness (LVPWs), and fractional shortening (FS) as observed by echocardiography (ISO+MA(PC6) vs. ISO groups: P<0.05). Moreover, evidence from morphological studies demonstrated that acupuncture at PC6 inhibited myocardial hypertrophy and collagen deposition, and normalised the ultrastructural changes. In addition, ANP and TNFα expression were attenuated in the verum acupuncture group compared with the untreated model group (ISO+MA(PC6) vs. ISO groups: P<0.05). CONCLUSIONS: The results demonstrated that acupuncture at PC6 attenuates sympathetic overactivity. Additionally, it may improve cardiac performance by reversing adverse cardiac remodelling. Acupuncture has potential as a treatment for sympathetic hypertension.


Assuntos
Terapia por Acupuntura , Cardiomegalia/terapia , Isoproterenol/efeitos adversos , Pontos de Acupuntura , Animais , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Modelos Animais de Doenças , Humanos , Injeções Subcutâneas , Isoproterenol/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Propranolol/administração & dosagem , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
Allergol Int ; 68(3): 335-341, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30846304

RESUMO

BACKGROUND: Although the guidelines in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma, lower dose of l-isoproterenol has been widely used in Japan. To determine whether the efficacy of low-dose l-isoproterenol was superior to that of salbutamol, we conducted a double-blind, randomized controlled trial. METHODS: Hospitalized patients aged 1-17 years were eligible if they had severe asthma exacerbation defined by the modified pulmonary index score (MPIS). Patients were randomly assigned (1:1) to receive inhalation of l-isoproterenol (10 µg/kg/h) or salbutamol (500 µg/kg/h) for 12 hours via a large-volume nebulizer with oxygen. The primary outcome was the change in MPIS from baseline to 3 hours after starting inhalation. Trial registration number UMIN000001991. RESULTS: From December 2009 to October 2013, 83 patients (42 in the l-isoproterenol group and 41 in the salbutamol group) were enrolled into the study. Of these, one patient in the l-isoproterenol group did not receive the study drug and was excluded from the analysis. Compared with salbutamol, l-isoproterenol reduced MPIS more rapidly. Mean (SD) changes in MPIS at 3 hours were -2.9 (2.5) in the l-isoproterenol group and -0.9 (2.3) in the salbutamol group (difference -2.0, 95% confidence interval -3.1 to -0.9; P < 0.001). Adverse events occurred in 1 (2%) and 11 (27%) patients in the l-isoproterenol and salbutamol groups, respectively (P = 0.003). Hypokalemia and tachycardia occurred only in the salbutamol group. CONCLUSIONS: Low-dose l-isoproterenol has a more rapid effect with fewer adverse events than salbutamol.


Assuntos
Albuterol/uso terapêutico , Asma/tratamento farmacológico , Asma/fisiopatologia , Broncodilatadores/uso terapêutico , Isoproterenol/uso terapêutico , Administração por Inalação , Albuterol/administração & dosagem , Albuterol/efeitos adversos , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Criança , Pré-Escolar , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Lactente , Isoproterenol/administração & dosagem , Isoproterenol/efeitos adversos , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Resultado do Tratamento
11.
Allergy Asthma Proc ; 40(2): 111-115, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30819280

RESUMO

Background: There are no validated quantitative tools for assessing asthma exacerbation, which may cause significant variation in determining the severity of exacerbation across caregivers. A modified Pulmonary Index Score (mPIS) has been proposed as a quantitative indicator of the severity of childhood asthma exacerbation. However, the utility of mPIS as a treatment decision-making tool has not been investigated. Objective: The aim of the present study was to clarify the utility of therapeutic strategies based on mPIS in children hospitalized for asthma exacerbation. Methods: This was a case-control study of patients admitted to our hospital between 2010 and 2015. In addition to the conventional therapy based on Japanese guidelines, treatment adaptation by using mPIS began in 2013. Children admitted after 2013 were regarded as being in the case group and those before 2012 were the control group. The length of the hospital stay and the duration of continuous isoproterenol inhalation therapy (CIT) were compared as clinical outcomes. Results: The targeted number of patients was 346 (182 cases and 164 controls). The mean ± standard error age was 3.5 ± 0.2 years in the case group and 3.4 ± 0.2 years in the control group. Male patients constituted 64.3% of the case group and 60.4% of the control group. The mean ± standard error length of hospital stay was significantly shortened in the case group (8.1 ± 0.2 days versus 9.6 ± 0.2 days, p < 0.001). The mean ± standard error duration of CIT was also shortened in the case group (2.3 ± 0.1 days versus 3.9 ± 0.3 days, p < 0.001). Conclusion: An mPIS-based therapeutic strategy may have reduced the length of hospital stay by enabling timely adjustments to clinical interventions and enabling caregivers to perform a more-accurate assessment of asthma exacerbation.


Assuntos
Asma/terapia , Índice de Gravidade de Doença , Administração por Inalação , Asma/diagnóstico , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Isoproterenol/administração & dosagem , Tempo de Internação , Masculino
12.
Eur Heart J Acute Cardiovasc Care ; 8(8): 775-776, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27154527

RESUMO

Torsades de pointes (TdP) is a fatal polymorphic ventricular tachycardia in association with congenital or acquired QT prolongation. Concomitant electrolyte disturbances and drugs potentiate the development of TdP. We describe a severe case of refractory TdP in the setting of methadone, cocaine, hypokalemia and hypomagnesemia. The successful treatment was achieved with the administration of magnesium, isoproterenol, and electrolyte replacement.


Assuntos
Benzodiazepinas/toxicidade , Cocaína/toxicidade , Síndrome do QT Longo/etiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Torsades de Pointes/diagnóstico , Administração Intravenosa , Antiarrítmicos/administração & dosagem , Antiarrítmicos/uso terapêutico , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Ecocardiografia Tridimensional/métodos , Eletrocardiografia/métodos , Feminino , Humanos , Hipercalciúria/diagnóstico , Hipopotassemia/diagnóstico , Infusões Intravenosas , Isoproterenol/administração & dosagem , Isoproterenol/uso terapêutico , Síndrome do QT Longo/fisiopatologia , Sulfato de Magnésio/administração & dosagem , Sulfato de Magnésio/uso terapêutico , Pessoa de Meia-Idade , Nefrocalcinose/diagnóstico , Potássio/administração & dosagem , Potássio/uso terapêutico , Erros Inatos do Transporte Tubular Renal/diagnóstico , Índice de Gravidade de Doença , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Simpatomiméticos/administração & dosagem , Simpatomiméticos/uso terapêutico , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/fisiopatologia , Resultado do Tratamento , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
13.
J Cardiovasc Electrophysiol ; 30(2): 171-177, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30375070

RESUMO

INTRODUCTION: Both isoproterenol (Iso) and adenosine (Ado) are used to induce atrial fibrillation (AF) in the electrophysiology lab. However, the utility of Ado has not been systematically established. OBJECTIVE: The purpose of this study was to compare Ado to Iso for the induction of paroxysmal AF. METHODS: Forty patients (16 women; mean age, 60 ± 12 years) with paroxysmal AF, presenting for ablation were prospectively included of whom 36 (90%) received Ado (18-36 mg) and/or Iso (3-20 µg/min incremental dose) in a randomized order (26 [72%] received both drugs). RESULTS: AF was induced with Iso in 15 of 32 (47%) and with Ado in 12 of 30 (40%) patients (P = 0.9). Iso-triggered AF started from the left pulmonary veins (PVs) in 11 of 15 (73%), from the right PVs in 3 of 15 (20%), and from the coronary sinus (CS) in 1 of 15 (7%) cases. Ado-induced AF episodes originated from the left PVs in 6 of 12 (50%), from the right atrium (RA) in 4 of 12 (33%), and from the CS in 2 of 12 (17%) cases. Altogether, Iso-induced AF was more likely initiated from the PVs (93%) compared with Ado (50%) ( P = 0.02). Ado-induced non-PV triggers were not predictive of arrhythmia recurrence after PV isolation. CONCLUSION: Ado much more frequently induces non-PV triggers, especially from the RA. The clinical significance of these foci, however, is questionable.


Assuntos
Adenosina/administração & dosagem , Agonistas Adrenérgicos beta/administração & dosagem , Fibrilação Atrial/diagnóstico , Seio Coronário/fisiopatologia , Técnicas Eletrofisiológicas Cardíacas , Isoproterenol/administração & dosagem , Veias Pulmonares/fisiopatologia , Agonistas do Receptor Purinérgico P1/administração & dosagem , Potenciais de Ação , Adenosina/efeitos adversos , Agonistas Adrenérgicos beta/efeitos adversos , Idoso , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Ablação por Cateter , Seio Coronário/cirurgia , Feminino , Frequência Cardíaca , Humanos , Isoproterenol/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Veias Pulmonares/cirurgia , Agonistas do Receptor Purinérgico P1/efeitos adversos , Reprodutibilidade dos Testes
14.
F1000Res ; 7: 374, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555684

RESUMO

Background: Two notable findings of clinically healthy feedlot cattle suggest they may have pulmonary hydrostatic edema during the finishing phase of production: increased pulmonary arterial wedge pressures and pulmonary venous hypertrophy. The goal of this study was to determine if increased pulmonary arterial wedge pressure (PAWP) in a Holstein calf could lead to diffuse alveolar damage consistent with the early, exudative phase of acute interstitial pneumonia of feedlot cattle. Methods: Six male Holstein dairy calves were given daily subcutaneous injections of the nonspecific ß-adrenergic agonist isoprenaline (10 mg/kg/d), to induce left ventricular diastolic dysfunction, or sterile water for 14 days. On Day 14, pulmonary arterial pressures and wedge pressures were measured, echocardiography performed, and the ratio of mitral valve flow velocity (E) to septal lengthening velocity (e') calculated. Calves were euthanized on Day 15 and lung lesions semi-quantitatively scored. Results: Mean PAWP was 12 ± 1 mm Hg in calves that received isoprenaline and 7 ± 1 mm Hg in controls ( P = 0.01). Calves that received isoprenaline tended to have greater relative wall thickness than control calves ( P = 0.15) and greater E/e' ratios ( P = 0.16), suggestive of concentric hypertrophy and diastolic dysfunction, respectively. Calves that received isoprenaline also tended to have a left ventricle and interventricular septum that was 29 ± 10 g heavier than control calves ( P = 0.10) when controlling for body mass. Hyaline membranes, the hallmark feature of diffuse alveolar damage, were evident in lung sections from all calves that received isoprenaline but none of the controls. Conclusions: Consistent with prior pathological and physiological studies of feedlot cattle, this study provides preliminary evidence that cattle presenting with clinical signs and pathology consistent with early stage acute interstitial pneumonia could be attributable to hydrostatic edema associated with left ventricular failure.


Assuntos
Hipertensão Pulmonar/veterinária , Alvéolos Pulmonares/patologia , Edema Pulmonar/etiologia , Edema Pulmonar/patologia , Disfunção Ventricular Esquerda/veterinária , Agonistas Adrenérgicos beta/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Bovinos , Modelos Animais de Doenças , Pressão Hidrostática , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/complicações , Isoproterenol/administração & dosagem , Masculino , Disfunção Ventricular Esquerda/complicações
15.
PLoS One ; 13(10): e0203602, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30273351

RESUMO

In order to determine the role of the adrenergic system in bupivacaine-induced cardiotoxicity, a series of experiments were performed. In an animal experiment, male Sprague-Dawley (SD) rats under chloral hydrate anesthesia received intravenous bupivacaine, followed by an intravenous injection of adrenalin or isoprenalin, and the electrocardiogram (ECG), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of rise of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease (-dP/dtmax) were continually monitored. In a cellular experiment, freshly isolated adult SD rat ventricular myocytes were perfused with bupivacaine at different concentrations in the presence or absence of isoprenalin, with or without esmolol. The percentage of the sarcomere shortening (bl% peak h), departure velocity (dep v) of sarcomere shortening and time to 50% of the peak speed of myocyte contraction (Tp50) was assessed by a video-based edge-detection system. In an additional experiment, Swiss mice pretreated with saline, isoprenalin, esmolol or dexmedetomidine received bupivacaine to determine the 50% lethal dose (LD50) of bupivacaine. Electron microscopy of myocardial mitochondria was performed to assess damage of these structures. To test mitochondrial reactive oxygen species (ROS) production, freshly isolated SD rat ventricular myocytes were incubated with bupivacaine in the presence of isoprenalin, with or without esmolol. First, our results showed that bupivacaine significantly reduced the LVSP and +dP/dtmax, as well as enhanced the LVEDP and -dP/dtmax (P < 0.05, vs. control, and vs. baseline). Adrenalin and isoprenalin induced a further reduction of LVSP and +dP/dtmax (P < 0.05, vs. before adrenalin or isoprenalin delivery, and vs. control). Second, bupivacaine induced a dose-dependent cardiomyocyte contractile depression. While 5.9 µmol/L or 8.9 µmol/L of bupivacaine resulted in no change, 30.0 µmol/L of bupivacaine prolonged the Tp50 and reduced the bl% peak h and dep v (P < 0.05, vs. control and vs. baseline). Isoprenalin aggravated the bupivacaine-induced cardiomyocyte contractile depression, significantly prolonging the Tp50 (P < 0.05, vs. bupivacaine alone) and reducing the dep v (P < 0.05, vs. bupivacaine alone). Third, esmolol and dexmedetomidine significantly enhanced, while isoprenalin significantly reduced, the LD50 of bupivacaine in mice. Fourth, bupivacaine led to significant mitochondrial swelling, and the extent of myocardial mitochondrial swelling in isoprenalin-pretreated mice was significantly higher than that compared with mice pretreated with saline, as reflected by the higher mitochondrial damage score (P < 0.01). Meanwhile, esmolol pretreatment significantly reduced the mitochondrial damage score (P < 0.01). Fifth, bupivacaine significantly increased the ROS in freshly isolated cardiomyocytes, and added isoprenalin induced a further enhancement of ROS production (P < 0.05, vs. bupivacaine alone). Added esmolol significantly decreased ROS production (P < 0.05, vs. bupivacaine + isoprenalin). Our results suggest that bupivacaine depressed cardiac automaticity, conductivity and contractility, but the predominant effect was contractile dysfunction which resulted from the disruption of mitochondrial energy metabolism. ß-adrenergic activation aggravated the cellular metabolism disorder and therefore contractile dysfunction.


Assuntos
Cardiotoxicidade/fisiopatologia , Epinefrina/administração & dosagem , Isoproterenol/administração & dosagem , Contração Miocárdica/efeitos dos fármacos , Anestesia/efeitos adversos , Animais , Pressão Sanguínea/efeitos dos fármacos , Bupivacaína/administração & dosagem , Bupivacaína/efeitos adversos , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Hidrato de Cloral/administração & dosagem , Modelos Animais de Doenças , Eletrocardiografia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Camundongos , Contração Miocárdica/fisiologia , Propanolaminas/administração & dosagem , Ratos , Espécies Reativas de Oxigênio/metabolismo
16.
EMBO Mol Med ; 10(9)2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30093491

RESUMO

Environmental enrichment (EE) is a rodent behavioral paradigm that can model the cognitive benefits to humans associated with intellectual activity and exercise. We recently discovered EE's anti-inflammatory protection of brain microglia against soluble oligomers of human amyloid ß-protein (oAß). Mechanistically, we report that the key factor in microglial protection by EE is chronically enhanced ß-adrenergic signaling. Quantifying microglial morphology and inflammatory RNA profiles revealed that mice in standard housing (SH) fed the ß-adrenergic agonist isoproterenol experienced similar protection of microglia against oAß-induced inflammation as did mice in EE Conversely, mice in EE fed the ß-adrenergic antagonist propranolol lost microglial protection against oAß. Mice lacking ß1/ß2-adrenergic receptors showed no protection of microglia by EE In SH mice, quantification of norepinephrine in hippocampus and interstitial fluid showed that oAß disrupted norepinephrine homeostasis, and microglial-specific analysis of ß2-adrenergic receptors indicated a decreased receptor level. Both features were rescued by EE Thus, enhanced ß-adrenergic signaling at the ligand and receptor levels mediates potent benefits of EE on microglial inflammation induced by human Aß oligomers in vivo.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Encefalite/prevenção & controle , Exposição Ambiental , Hipocampo/patologia , Microglia/efeitos dos fármacos , Receptores Adrenérgicos beta/metabolismo , Transdução de Sinais , Agonistas Adrenérgicos beta/administração & dosagem , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Isoproterenol/administração & dosagem , Camundongos , Microglia/patologia
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(6): 508-513, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29972128

RESUMO

OBJECTIVE: To explore the feasibility of intraperitoneal injection of isoproterenol (ISO) to induce cardiac remodeling in FVB/N mice. METHODS: Forty-eight FVB/N mice were divided into back subcutaneous saline group (subcutaneous saline group), intraperitoneal saline group, back subcutaneous ISO group (subcutaneous ISO group), and intraperitoneal ISO group according to the route of administration of saline or ISO. ISO (30 µg/g body weight/day) was given to the subcutaneous ISO group and the intraperitoneal ISO group, twice daily with an interval of 12 hours, for 14 consecutive days. The subcutaneous saline group and the intraperitoneal saline group were injected with an equal volume of saline. The left ventricular end-diastolic posterior wall thickness was measured by echocardiography, and the ratio of heart weight to tibia length was determined. Hematoxylin-eosin staining was used to determine the myocardial fiber diameter. Picric-sirius red staining was used to determine the myocardial collagen deposition area. Quantitative real-time PCR was used to measure the mRNA expression of collagen I. RESULTS: Compared with the subcutaneous ISO, subcutaneous saline, and intraperitoneal saline groups, the intraperitoneal ISO group had increased sizes of the cardiac cavity and the heart. Compared with the subcutaneous saline and intraperitoneal saline groups, the subcutaneous ISO group showed no significant changes in the gross morphology of the cardiac cavity and the heart. The intraperitoneal ISO group showed significant increases in the ratio of heart weight to tibia length, myocardial fiber diameter, left ventricular end-diastolic posterior wall thickness, myocardial collagen area percentage, and the mRNA expression of collagen I compared with the subcutaneous ISO, subcutaneous saline, and intraperitoneal saline groups (P<0.01). There were no significant differences in the above five indices between the subcutaneous ISO group and the subcutaneous saline and intraperitoneal saline groups (P>0.05). No significant difference in the mortality rate was found between the subcutaneous ISO and intraperitoneal ISO groups (P>0.05). CONCLUSIONS: Intraperitoneal injection of ISO can induce cardiac hypertrophy and fibrosis in FVB/N mice.


Assuntos
Remodelamento Atrial/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Isoproterenol/administração & dosagem , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Colágeno/metabolismo , Modelos Animais de Doenças , Humanos , Injeções Intraperitoneais , Masculino , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia
18.
G Ital Cardiol (Rome) ; 19(4): 239-241, 2018 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-29912238

RESUMO

Takotsubo syndrome (TTS) is an acute cardiac syndrome characterized by transient systolic left ventricular dysfunction frequently preceded by stressful events. It typically affects postmenopausal women without angiographic evidence of obstructive coronary artery disease. We report here an uncommon occurrence of secondary TTS in a male with coronary artery disease after exogenous catecholamine administration and pacemaker implantation. This unexpected case suggests that, in such clinical scenario, a TTS diagnosis might be considered even in unsuspected individuals.


Assuntos
Doença da Artéria Coronariana/terapia , Isoproterenol/efeitos adversos , Marca-Passo Artificial/efeitos adversos , Cardiomiopatia de Takotsubo/etiologia , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Eletrocardiografia/métodos , Humanos , Isoproterenol/administração & dosagem , Itália , Masculino , Doenças Raras , Medição de Risco , Cardiomiopatia de Takotsubo/diagnóstico por imagem , Cardiomiopatia de Takotsubo/fisiopatologia
19.
J Cell Biochem ; 119(9): 7300-7309, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29761924

RESUMO

The response to glucagon and adrenaline in cancer cachexia is poorly known. The aim of this study was to investigate the response to glucagon, adrenergic agonists (α and ß) and cyclic adenosine monophosphate (cAMP) on glycogenolysis, gluconeogenesis, and glycolysis in liver perfusion of Walker-256 tumor-bearing rats with advanced cachexia. Liver ATP content was also investigated. Rats without tumor (healthy) were used as controls. Agonists α (phenylephrine) and ß (isoproterenol) adrenergic, instead of adrenaline, and cAMP, the second messenger of glucagon and isoproterenol, were used in an attempt to identify mechanisms involved in the responses. Glucagon (1 nM) stimulated glycogenolysis and gluconeogenesis and inhibited glycolysis in the liver of healthy and tumor-bearing rats, but their effects were lower in tumor-bearing rats. Isoproterenol (20 µM) stimulated glycogenolysis, gluconeogenesis, and glycolysis in healthy rats and had virtually no effect in tumor-bearing rats. cAMP (9 µM) also stimulated glycogenolysis and gluconeogenesis and inhibited glycolysis in healthy rats but had practically no effect in tumor-bearing rats. Phenylephrine (2 µM) stimulated glycogenolysis and gluconeogenesis and inhibited glycolysis and these effects were also lower in tumor-bearing rats than in healthy. Liver ATP content was lower in tumor-bearing rats. In conclusion, tumor-bearing rats with advanced cachexia showed a decreased hepatic response to glucagon, adrenergic agonists (α and ß), and cAMP in glycogenolysis, gluconeogenesis, and glycolysis, which may be due to a reduced rate of regulatory enzyme phosphorylation caused by the low ATP levels in the liver.


Assuntos
Agonistas Adrenérgicos/farmacologia , AMP Cíclico/farmacologia , Glucagon/farmacologia , Gluconeogênese , Glicogenólise , Glicólise , Fígado/metabolismo , Neoplasias/metabolismo , Trifosfato de Adenosina/metabolismo , Agonistas Adrenérgicos/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/farmacologia , Animais , Caquexia/etiologia , Caquexia/metabolismo , AMP Cíclico/administração & dosagem , Glucagon/administração & dosagem , Isoproterenol/administração & dosagem , Isoproterenol/farmacologia , Masculino , Neoplasias/complicações , Perfusão/métodos , Fenilefrina/administração & dosagem , Fenilefrina/farmacologia , Ratos , Ratos Wistar
20.
Neurobiol Learn Mem ; 151: 71-84, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29653257

RESUMO

The hippocampus is a functionally heterogeneous structure with the cognitive and emotional signal processing ascribed to the dorsal (DH) and the ventral hippocampus (VH) respectively. However, the underlying mechanisms are poorly understood. Noradrenaline is released in hippocampus during emotional arousal modulating synaptic plasticity and memory consolidation through activation of ß adrenergic receptors (ß-ARs). Using recordings of field excitatory postsynaptic potentials from the CA1 field of adult rat hippocampal slices we demonstrate that long-term potentiation (LTP) induced either by theta-burst stimulation (TBS) that mimics a physiological firing pattern of hippocampal neurons or by high-frequency stimulation is remarkably more sensitive to ß-AR activation in VH than in DH. Thus, pairing of subthreshold primed burst stimulation with activation of ß-ARs by their agonist isoproterenol (1 µM) resulted in a reliable induction of NMDA receptor-dependent LTP in the VH without affecting LTP in the DH. Activation of ß-ARs by isoproterenol during application of intense TBS increased the magnitude of LTP in both hippocampal segments but facilitated voltage-gated calcium channel-dependent LTP in VH only. Endogenous ß-AR activation contributed to the stabilization and the magnitude of LTP in VH but not DH as demonstrated by the effects of the ß-ARs antagonist propranolol (10 µM). Exogenous (but not endogenous) ß-AR activation strongly increased TBS-induced facilitation of postsynaptic excitability in VH. In DH, isoproterenol only produced a moderate and GABAergic inhibition-dependent enhancement in the facilitation of synaptic burst responses. Paired-pulse facilitation did not change with LTP at any experimental condition suggesting that expression of LTP does not involve presynaptic mechanisms. These findings suggest that ß-AR may act as a switch that selectively promotes synaptic plasticity in VH through multiple ways and provide thus a first clue to mechanisms that underlie VH involvement in emotionality.


Assuntos
Hipocampo/fisiologia , Potenciação de Longa Duração , Receptores Adrenérgicos beta/fisiologia , Agonistas Adrenérgicos beta/administração & dosagem , Animais , Estimulação Elétrica , Hipocampo/efeitos dos fármacos , Isoproterenol/administração & dosagem , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ratos Wistar , Receptores de N-Metil-D-Aspartato/fisiologia
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