Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.310
Filtrar
2.
J Ethnopharmacol ; 246: 112154, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31415848

RESUMO

Treating ventricular remodeling continues to be a clinical challenge. Studies have shown that hypertension is one of the most common causes of ventricular remodeling, and is a major cause of cardiovascular risk in adults. Here, we report that Tongsaimai (TSM), a Chinese traditional medicine, could inhibit arterial pressure and left ventricular pressure to improve hemodynamic abnormalities in rats impaired by abdominal aortic constriction (AAC). Administration of TSM significantly reduced the heart mass index and the left ventricular mass index significantly in AAC rats. TSM could also markedly ameliorate cardiac collagen deposition and reduce the concentration of hydroxyproline in the heart of AAC rats. Moreover, TSM alleviated cardiac histomorphology injury resulting from AAC, including reducing cardiomyocyte hypertrophy, fibrous connective tissue hyperplasia, cardiomyocyte apoptosis, replacement fibrosis and the disorders of myocardial myofibrils, intercalated discs, mitochondria and mitochondrial crista. In addition, the levels of transforming growth factor (TGF) - ß and inflammation-related molecules including tumor necrosis factor-α (TNF-α), which were over-expressed with AAC, were decreased by STM. In conclusion, STM could reverse the hypertension and left ventricular remolding caused by abdominal aortic constriction in rats.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Animais , Anti-Hipertensivos/farmacologia , Aorta Abdominal , Pressão Arterial/efeitos dos fármacos , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Colágeno/metabolismo , Constrição , Hipertensão/metabolismo , Hipertensão/patologia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Ratos Sprague-Dawley , Sistema Renina-Angiotensina/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
Acta Cir Bras ; 34(9): e201900905, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800679

RESUMO

PURPOSE: To investigate efficacy of combined use of parecoxib and dexmedetomidine on postoperative pain and early cognitive dysfunction after laparoscopic cholecystectomy for elderly patients. METHODS: The present prospective randomized controlled study included a total of 80 patients who underwent laparoscopic cholecystectomy surgery during January 2016 to November 2017 in our hospital. All patients were randomly divided into 4 groups, the parecoxib group, the dexmedetomidine group, the parecoxib and dexmedetomidine combined group, and the control group. Demographic data and clinical data were collected. Indexes of heart rate (HR), mean arterial pressure (MAP), levels of jugular venous oxygen saturation (SjvO2) and jugular venous oxygen pressure (PjvO2) were recorded at different time points before and during the surgery. The mini-mental state examination (MMSE) score, Ramsay score and Visual Analogue Score (VAS) were measured. RESULTS: Levels of both SjvO2 and PjvO2 were significantly higher in parecoxib group, dexmedetomidine group and the combined group than the control group. Meanwhile, levels of both SjvO2 and PjvO2 in the combined group were the highest. VAS scores were significantly lower in the combined group than all other groups, and total patient controlled intravenous analgesia (PCIA) pressing times within 48 h after surgery were the lowest in the combined group. Both Ramsay and MMSE scores were the highest in the combined group compared with other groups, while were the lowest in the control group. CONCLUSION: The combined use of parecoxib and dexmedetomidine could reduce the postoperative pain and improve the postoperative sedation and cognitive conditions of patients after laparoscopic cholecystectomy.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Colecistectomia Laparoscópica/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Dexmedetomidina/administração & dosagem , Isoxazóis/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , /tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Pressão Arterial/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
4.
Medicine (Baltimore) ; 98(46): e17957, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725655

RESUMO

BACKGROUND: Although surgical field visualization is important in functional endoscopic sinus surgery (FESS), the complications associated with controlled hypotension for surgery should be considered. Intraoperative hypotension is associated with postoperative stroke, leading to subsequent hypoxia with potential neurologic injury. We investigated the effect of propofol and desflurane anesthesia on S-100ß and glial fibrillary acidic protein (GFAP) levels which are early biomarkers for cerebral ischemic change during controlled hypotension for FESS. METHODS: For controlled hypotension during FESS, anesthesia was maintained with propofol/remifentanil in propofol group (n = 30) and with desflurane/remifentanil in desflurane group (n = 30). For S-100ß and GFAP assay, blood samples were taken at base, 20 and 60 minutes after achieving the target range of mean arterial pressure, and at 60 minutes after surgery. RESULTS: The base levels of S-100ß were 98.04 ±â€Š78.57 and 112.61 ±â€Š66.38 pg/mL in the propofol and desflurane groups, respectively. The base levels of GFAP were 0.997 ±â€Š0.486 and 0.898 ±â€Š0.472 ng/mL in the propofol and desflurane groups, respectively. The S-100ß and GFAP levels were significantly increased in the study period compared to the base levels in both groups (P ≤ .001). There was no significant difference at each time point between the 2 groups. CONCLUSION: On comparing the effects of propofol and desflurane anesthesia for controlled hypotension on the levels of S-100ß and GFAP, we noted that there was no significant difference in S-100ß and GFAP levels between the 2 study groups. CLINICAL TRIAL REGISTRATION: Available at: http://cris.nih.go.kr, KCT0002698.


Assuntos
Proteína Glial Fibrilar Ácida/sangue , Hipotensão Controlada/métodos , Propofol/uso terapêutico , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Sinusite/cirurgia , Adulto , Anestésicos Intravenosos , Pressão Arterial/efeitos dos fármacos , Dióxido de Carbono/sangue , Doença Crônica , Desflurano/administração & dosagem , Desflurano/efeitos adversos , Desflurano/uso terapêutico , Endoscopia , Feminino , Proteína Glial Fibrilar Ácida/biossíntese , Humanos , Hipotensão Controlada/efeitos adversos , Masculino , Pessoa de Meia-Idade , Propofol/administração & dosagem , Propofol/efeitos adversos , Estudos Prospectivos , Remifentanil/administração & dosagem , Subunidade beta da Proteína Ligante de Cálcio S100/biossíntese , Fatores de Tempo
6.
Hypertension ; 74(4): 896-902, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31378100

RESUMO

Early and preferential activation of cardiac sympathetic nerve activity (CSNA) is one of the strongest prognostic markers of heart failure (HF) in patients. Our previous studies have implicated central angiotensin mechanisms as playing a critical role in generating this increase in cardiac sympathetic drive. However, it is unclear if inhibition of AT1R (angiotensin type-1 receptors) in different neural groups in the sympathetic pathway to the heart, such as the sympathetic preganglionic neurons in the intermediolateral column of the spinal cord, can reduce cardiac sympathetic drive. We hypothesized that in HF, localized intrathecal administration of the AT1R antagonist losartan, specifically into the T1-2 subarachnoid space, would decrease CSNA. In normal conscious sheep, intrathecal infusion of Ang II (angiotensin II; 3.0 nmol/mL per hour), significantly increased mean arterial pressure and CSNA; this effect was abolished by prior administration of losartan (1 mg/h). In an ovine rapid ventricular pacing model of HF, the resting levels of heart rate and CSNA were significantly elevated compared with normals. Intrathecal infusion of losartan (1 mg/h) in HF significantly reduced CSNA and heart rate but did not change arterial pressure. The AT1R binding density in the spinal cord was also elevated in the HF group. Our data suggest that AT1Rs within the spinal cord are responsible, in part, for the increased CSNA in HF and may represent a target for the selective reduction of CSNA in HF.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Gânglios Simpáticos/efeitos dos fármacos , Insuficiência Cardíaca/fisiopatologia , Losartan/administração & dosagem , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Pressão Arterial/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Feminino , Gânglios Simpáticos/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Injeções Espinhais , Ovinos , Sistema Nervoso Simpático/fisiopatologia
7.
Nutrients ; 11(9)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438636

RESUMO

The close relationship between hypertension and dietary sodium intake is widely recognized and supported by several studies. A reduction in dietary sodium not only decreases the blood pressure and the incidence of hypertension, but is also associated with a reduction in morbidity and mortality from cardiovascular diseases. Prolonged modest reduction in salt intake induces a relevant fall in blood pressure in both hypertensive and normotensive individuals, irrespective of sex and ethnic group, with larger falls in systolic blood pressure for larger reductions in dietary salt. The high sodium intake and the increase in blood pressure levels are related to water retention, increase in systemic peripheral resistance, alterations in the endothelial function, changes in the structure and function of large elastic arteries, modification in sympathetic activity, and in the autonomic neuronal modulation of the cardiovascular system. In this review, we have focused on the effects of sodium intake on vascular hemodynamics and their implication in the pathogenesis of hypertension.


Assuntos
Hipertensão/induzido quimicamente , Sódio na Dieta/administração & dosagem , Sódio na Dieta/efeitos adversos , Pressão Arterial/efeitos dos fármacos , Pressão Arterial/fisiologia , Artérias/efeitos dos fármacos , Artérias/fisiologia , Humanos , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Rigidez Vascular/efeitos dos fármacos , Rigidez Vascular/fisiologia
8.
Int J Rheum Dis ; 22(9): 1775-1781, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31368254

RESUMO

AIM: This study aimed to retrospectively describe 15 new primary Sjögren's syndrome-pulmonary arterial hypertension (pSS-PAH) cases confirmed by right heart catheterization (RHC). Demographic and clinical characteristics were analyzed and risk factors for PAH in pSS were explored. METHOD: We retrospectively described 15 new pSS-PAH cases confirmed by RHC referred to our institution between January 2013 and March 2018. We present PAH and pSS characteristics, hemodynamic evaluations, medical management, and outcomes. A matched case control study was carried out to determine the risk factors of PAH in pSS compared with pSS-non-PAH patients. RESULTS: All patients were female with a mean age at PAH diagnosis of 52.9 ± 14.6 years. The delay between the first symptom and PAH diagnosis was 18.7 ± 19.7 months. The most common primary manifestation at PAH onset was exertional dyspnea (13/15). At diagnosis of PAH, PAH was severe with a mean pulmonary artery pressure of 48.8 ± 13.7 mm Hg (range, 27-72 mm Hg) and a mean cardiac index of 2.3 ± 0.6 L/min/m2 (range, 1.47-3.41 L/min/m2 ). Compared with the pSS-PAH without pericardial effusion, pSS-PAH with pericardial effusion had larger right arterial (53 [45-56.75] vs 38 [35.5-46.5], P = .018) and right ventricular sizes (47 [42.75-51.25] vs 36 [32.5-41], P = .007). Compared with the pSS non-PAH group, we identified 2 risk factors for PAH in pSS: pericardial effusion (odds ratio [OR] [95% CI], 14.29 [1.14-166.67], P = .039) and liver involvement (OR [95% CI], 14.71 [1.14-166.67], P = .035). CONCLUSION: For pSS patients, PAH can be the first manifestation. We believe that systemic evaluation, especially in patients with pericardial effusion and liver involvement, is important to identify high-risk patients for PAH, improving their prognosis.


Assuntos
Pressão Arterial , Artéria Pulmonar/fisiopatologia , Síndrome de Sjogren/complicações , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , China , Dispneia/etiologia , Dispneia/fisiopatologia , Feminino , Humanos , Imunossupressores/uso terapêutico , Hepatopatias/etiologia , Hepatopatias/fisiopatologia , Pessoa de Meia-Idade , Derrame Pericárdico/etiologia , Derrame Pericárdico/fisiopatologia , Prognóstico , /tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico
9.
Hypertension ; 74(4): 910-920, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31422690

RESUMO

Hypertension is associated with increased sympathetic activity. A component of this sympathoexcitation may be driven by increased signaling from sensory endings from the heart to the autonomic control areas in the brain. This pathway mediates the so-called cardiac sympathetic afferent reflex, which is also activated by coronary ischemia or other nociceptive stimuli in the heart. The cardiac sympathetic afferent reflex has been shown to be enhanced in the heart failure state and in renal hypertension. However, little is known about its role in the development or progression of hypertension or the phenotype of the sensory endings involved. To investigate this, we used the selective afferent neurotoxin, resiniferatoxin (RTX) to chronically abolish the cardiac sympathetic afferent reflex in 2 models of hypertension; the spontaneous hypertensive rats (SHRs) and AngII (angiotensin II) infusion (240 ng/kg per min). Blood pressure (BP) was measured in conscious animals for 2 to 8 weeks post-RTX. Epidural application of RTX to the T1-T4 spinal segments prevented the further BP increase in 8-week-old SHR and lowered BP in 16-week-old SHR. RTX did not affect BP in Wistar-Kyoto normotensive rats nor in AngII-infused rats. Epicardial application of RTX (50 µg/mL) in 4-week-old SHR prevented the BP increase whereas this treatment does not lower BP in 16-week-old SHR. When RTX was administered into the L2-L5 spinal segments of 16-week-old SHR, no change in BP was observed. These findings indicate that signaling via thoracic afferent nerve fibers may contribute to the hypertension phenotype in the SHR but not in the Ang II infusion model of hypertension.


Assuntos
Pressão Sanguínea/fisiologia , Gânglios Espinais/metabolismo , Coração/inervação , Hipertensão/metabolismo , Canais de Cátion TRPV/agonistas , Angiotensina II , Animais , Pressão Arterial/efeitos dos fármacos , Pressão Arterial/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Diterpenos/farmacologia , Gânglios Espinais/efeitos dos fármacos , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hipertensão/induzido quimicamente , Masculino , Neurotoxinas/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Reflexo/efeitos dos fármacos , Reflexo/fisiologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo
10.
Hypertension ; 74(4): 921-928, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31446803

RESUMO

Clustering of arterial blood pressure (BP) waveform parameters could summarize complex information into distinct elements, which could be used to investigate cumulative (nonredundant) associations. We investigated this hypothesis in a large, adult population-based study (ViDA trial [Vitamin D Assessment] trial). To interpret the clusters and evaluate their usefulness, we examined their predictors and associations with cardiovascular events. In 4253 adults (mean age 65 years; 55% male) without a prior cardiovascular event, suprasystolic oscillometry was performed, yielding aortic pressure waveforms and several hemodynamic parameters. Participants were followed up for 4.6 years (median), accruing 300 cardiovascular events. Principal component analysis reduced 14 arterial waveform parameters to 3 uncorrelated factors that together explained 90% of the variability of the original data. Factors 1, 2, and 3 appeared to represent BP pulsatility, mean BP, and wave reflection, respectively. Across 6 antihypertensive drug classes, there were no differences in brachial systolic (P=0.23) and diastolic (P=0.13) BP; but there were significant variations in factor 3 (P<0.0001), especially for ß-blocker use. The first and third factors were positively associated with cardiovascular events (multivariable-adjusted standardized hazard ratio [95% CI]=1.33 [1.18-1.50] and 1.15 [1.02-1.30], respectively), whereas the second factor had a J-shaped relationship, with a nadir corresponding to a brachial diastolic BP of ≈75 mm Hg. In conclusion, BP pulsatility, mean BP, and wave reflection are prognostically meaningful, distinct aspects of arterial function that can be used to summarize physiological variations in multiple arterial waveform parameters and identify truly cumulative associations when used as cardiovascular risk outcomes.


Assuntos
Pressão Arterial/fisiologia , Artéria Braquial/fisiopatologia , Hipertensão/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Feminino , Hemodinâmica , Humanos , Hipertensão/tratamento farmacológico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso
11.
World Neurosurg ; 132: e834-e840, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31404696

RESUMO

BACKGROUND: Current guidelines recommend the administration of nimodipine for the prevention of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, nimodipine can lead to significant drops in mean arterial pressure and cerebral perfusion pressure. Catecholamines are then used to maintain them while nimodipine is reduced and/or held. There is no evidence that nimodipine retains its neuroprotective effect at lower doses. We aimed to investigate the role of nimodipine interruption in the setting of aSAH and its possible impact on the incidence of DCI. METHODS: We performed a retrospective analysis in patients with aSAH admitted to our center from January 2012 to October 2015. Nimodipine prophylaxis duration and dosage and the incidence of DCI were recorded. Bivariate correlation with Spearman's rho (ρ) and ordinal regression analyses were performed. RESULTS: A total of 170 patients were included in the study. Of these, 165 (97.1%) received nimodipine prophylaxis starting on day 0. Nimodipine was interrupted in 85 of 165 (51.5%), whereas dose was reduced in 47 of 165 (28.5%); full dose was received by only 33 of 165 (20%). DCI was observed in 85 of 170 (50%). Nimodipine interruption correlated in a statistically significant way with a greater incidence of DCI (ρ = 0.431, P < 0.001); receiving full doses of nimodipine showed a statistically significant inverse correlation to DCI (ρ = -0.273, P < 0.001). Ordinal regression analysis revealed nimodipine interruption as a statistically significant independent predictor of DCI (odds ratio 0.194; 95% confidence interval 0.079-0.474, P < 0.001). CONCLUSIONS: Our analysis reveals a greater incidence of DCI in patients with aSAH when nimodipine is interrupted.


Assuntos
Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Catecolaminas/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Nimodipina/administração & dosagem , Nimodipina/uso terapêutico , Hemorragia Subaracnóidea/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Arterial/efeitos dos fármacos , Isquemia Encefálica/prevenção & controle , Circulação Cerebrovascular/efeitos dos fármacos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/efeitos adversos , Nimodipina/efeitos adversos , Estudos Retrospectivos
12.
Nutr. hosp ; 36(4): 905-911, jul.-ago. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-184717

RESUMO

Introduction: therapeutic lifestyles changes including frequent consumption of legumes have resulted in improved metabolic control and decreased blood pressure in type 2 diabetes-mellitus (T2DM) patients. Objective: this was a quasi-experimental-28-week crossover-study that assessed the effect of daily consumption of the legume Lupinus mutabilis (LM) on metabolic control of T2DM patients under hypoglycemic oral treatment. Material and methods: we recruited 79 adult male and female patients that were followed for 14-weeks without LM consumption and then received increasing doses of a LM-based-snack for other 14-weeks. Results: there was a significant decrease in blood pressure and a significant increase in HDL-cholesterol by the end of the study period. While patients with A1C concentrations > 8 and ≤ 10 did not significantly improve their metabolic control, patients with serum A1C concentrations ≤ 8.0% reduced significantly their A1C after the intervention and 71% achieved a target concentration of 6.5%. Conclusion: patients with T2DM could benefit with the addition of LM-snack to their conventional treatment


Introducción: los cambios recomendados sobre los estilos de vida, incluido el consumo frecuente de leguminosas, han resultado en un mejor control metabólico y disminución de la presión arterial en pacientes con diabetes mellitus tipo 2 (DMT2). Objetivo: este fue un estudio casi experimental cruzado de 28 semanas que evaluó el efecto del consumo diario de la leguminosa Lupinus mutabilis Sweet (LM) en el control metabólico de pacientes con DMT2 con tratamiento oral hipoglucemiante. Material y métodos: inicialmente se reclutaron 79 pacientes adultos, hombres y mujeres, que fueron seguidos durante 14 semanas sin consumo de LM y luego recibieron dosis crecientes de un tentempié de LM durante otras 14 semanas. Resultados: se observó una disminución significativa en la presión arterial y un aumento significativo en el colesterol-HDL después del consumo de LM. Mientras que los pacientes con concentraciones de A1C sérica > 8 y ≤ 10 no mejoraron significativamente su control metabólico, los pacientes con concentraciones séricas de A1C ≤ 8,0% redujeron significativamente su A1C después de la intervención y el 71% de estos pacientes llegó a la meta de tratamiento ≤ 6,5%. Conclusión: los pacientes con DMT2 podrían beneficiarse con la adición de un tentempié de LM a su tratamiento convencional


Assuntos
Humanos , Masculino , Feminino , Adulto , Diabetes Mellitus Tipo 2/dietoterapia , Lupinus , Resultado do Tratamento , Fabaceae , Lanches , Fitoterapia , Valor Nutritivo , Hipoglicemiantes/administração & dosagem , HDL-Colesterol/metabolismo , Pressão Arterial/efeitos dos fármacos , Gluconeogênese , Índice Glicêmico , Equador , Antropometria , Proteínas na Dieta , Sementes
13.
Korean J Intern Med ; 34(4): 696-707, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31272141

RESUMO

Pulmonary arterial hypertension (PAH) is characterized by remodeling of the distal pulmonary arteries resulting in high pulmonary vascular resistance and, eventually, right ventricular heart failure. Although current advances in PAH therapy have improved outcomes, poor survival remains a reality worldwide, including Korea. One of the most important issues in PAH is the late diagnosis, since screening or diagnostic efforts are often overlooked due to the rarity of disease. Data from Korean registries and observational cohorts show that delayed detection leads to increased morbidity. Additionally, low percentages of Korean patients are committed to intensive PAH-targeted therapy. Current Korean health insurance policies' lack of coverage for new PAH-targeted drugs and upfront combination therapy may also hamper the improvement of treatment outcomes. Understanding individual variability in response to therapeutics through deep phenotyping is a novel strategy that should be considered when treating PAH. Overall, early detection of PAH by proactive screening together with early, intensive, individualized PAH therapy using deep phenotyping is crucial for improving prognoses for PAH patients in Korea.


Assuntos
Anti-Hipertensivos/uso terapêutico , Artéria Pulmonar/efeitos dos fármacos , Adulto , Idoso , Anti-Hipertensivos/efeitos adversos , Pressão Arterial/efeitos dos fármacos , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , /epidemiologia , Artéria Pulmonar/fisiopatologia , República da Coreia/epidemiologia , Fatores de Risco , Resultado do Tratamento , Remodelação Vascular/efeitos dos fármacos , Adulto Jovem
14.
Hypertension ; 74(3): 623-629, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31352825

RESUMO

Primary aldosteronism (PA) is hemodynamically independently associated with arterial wall stiffness as assessed by pulse wave velocity (PWV) compared with essential hypertension. Arterial wave reflection parameters derived from pulse wave analysis, such as forward and backward wave amplitudes (Pf and Pb), are promising vascular markers to predict cardiovascular outcomes in addition to PWV. These vascular parameters have never been studied in patients with PA before. In study part A, we prospectively enrolled 67 patients with PA and 132 patients with essential hypertension. In study part B, another 54 patients with PA were enrolled. Heart-carotid PWV was measured, and carotid pressure waveforms were recorded to calculate Pf, Pb, and augmentation index at baseline (part A and B) and 6 months after treatment (part B). The results showed that the patients with PA had significantly higher Pf (P=0.001), Pb (P=0.01), and PWV (P=0.021) than the patients with essential hypertension. In univariate correlation analysis, both log Pf and Pb were significantly correlated with age, office blood pressure, serum potassium level, log PWV, and the presence of PA. However, only Pb was significantly correlated with log plasma renin activity and log aldosterone to renin ratio. In multivariate analysis, log Pf was significantly correlated with the presence of PA (P=0.001), male sex, age, and mean arterial blood pressure. Pb was significantly correlated with the presence of PA (P=0.031), age, and mean arterial pressure. Six months after treatment, Pf and Pb decreased significantly. In conclusion, the patients with PA had significantly increased wave reflections compared with the patients with essential hypertension. Our results provide clinical evidence of aldosterone-related extensive vascular dysfunction of the arterial system.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Essencial/diagnóstico , Hipertensão Essencial/tratamento farmacológico , Hiperaldosteronismo/complicações , Hipertensão/tratamento farmacológico , Adulto , Aldosterona/sangue , Anti-Hipertensivos/farmacologia , Área Sob a Curva , Pressão Arterial/efeitos dos fármacos , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão/etiologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Onda de Pulso , Medição de Risco , Estatísticas não Paramétricas , Resultado do Tratamento , Adulto Jovem
15.
Eur J Pharmacol ; 858: 172447, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31228454

RESUMO

Mirabegron is the first ß3-adrenoceptor agonist approved on the market and may offer beneficial pharmacological action in patients with overactive bladder and erectile dysfunction. Here, we further investigate the mechanisms by which mirabegron induces rat corpus cavernosum (CC) relaxation. Adult male Wistar rats were used. The CC were isolated for in vitro functional assays and ß-adrenoceptors subtypes mRNA expression evaluation. Animals were treated orally with mirabegron (30 mg/kg, 3 h), tadalafil (10 mg/kg, 3 h) or both for intracavernous pressure (ICP). Intracellular levels of cAMP and cGMP were also determined. The ß1-, ß2- and ß3-adrenoceptors subtypes were expressed in rat CC. Mirabegron produced concentration-dependent CC relaxations that were unaffected by the ß1-, ß2- or ß3-adrenoceptor antagonists atenolol (1 µM), ICI-118,551 (1 µM) and L748,337 (10 µM), respectively. Mirabegron-induced relaxations were not affected by the phosphodiesterase type 4 inhibitor, rolipram, or the adenylyl cyclase selective inhibitor, SQ 22,536. Potassium channel- or calcium influx-blockade are not involved in mirabegron-induced relaxations. In contrast, mirabegron produced rightward shifts in the contractile response induced by the α1-adrenoceptor agonist, phenylephrine. Finally, cavernous nerve stimulation caused frequency-dependent ICP increases, which were significantly increased in rats treated with mirabegron in a similar degree of tadalafil-treated rat, without promoting a significant cAMP or cGMP accumulation. Together, our results demonstrate that mirabegron induced CC relaxation through α1-adrenoceptor blockade. Care should be taken to translate the effect of mirabegron into the clinic, especially when using rat as an animal model of erectile dysfunction.


Assuntos
Acetanilidas/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Ereção Peniana/efeitos dos fármacos , Pênis/efeitos dos fármacos , Pênis/fisiologia , Tiazóis/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Masculino , Contração Muscular/efeitos dos fármacos , Pênis/citologia , Pênis/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores Adrenérgicos beta/genética
16.
J Vasc Res ; 56(4): 204-214, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31189158

RESUMO

The reduced expression and function of voltage-dependent potassium (KV) channels have been involved in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH), leading to pulmonary vasoconstriction and vascular remodeling, while the upregulation of KV channels is of therapeutic significance for pulmonary hypertension. Beraprost sodium (BPS) has been shown to be effective in patients with pulmonary hypertension. However, the effect of BPS on O2-sensitive KV channels in pulmonary artery smooth muscle cells (PASMCs) remains unclear. In the present study, the effect of BPS on rats with HPH was observed, and the influence of BPS on the expression and function of O2-sensitive KV channels in PASMCs was investigated. The results revealed that BPS reduced mean pulmonary artery pressure, suppressed right ventricular hypertrophy, and attenuated the remodeling of pulmonary arteries in rats exposed to discontinuous hypoxia for 4 weeks (8 h/day). This was accompanied with the significantly upregulated expression of KV channel α-subunits (KV1.2, KV1.5 and KV2.1) and O2-sensitive voltage-gated K+ (KV) channel current (IK(V)) in small pulmonary arteries in HPH model rats, as well as in hypoxia-induced PASMCs. Furthermore, in vitrostudies have revealed that the upregulation of BPS on O2-sensitive KV channels was significantly inhibited after treatment with prostaglandin E2 receptor subtype EP4 antagonist GW627368X. Taken together, these results suggest that BPS attenuates the development of HPH through the upregulation of O2-sensitive KV channels, which was probably via the EP4 receptor-related pathway.


Assuntos
Anti-Hipertensivos/farmacologia , Epoprostenol/análogos & derivados , Hipóxia/complicações , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Receptores de Prostaglandina E Subtipo EP4/agonistas , Vasodilatadores/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Epoprostenol/farmacologia , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/metabolismo , Oxigênio/metabolismo , /fisiopatologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Ratos Sprague-Dawley , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Transdução de Sinais , Regulação para Cima , Remodelação Vascular/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos
17.
Andrologia ; 51(9): e13344, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31206753

RESUMO

To investigate whether low androgen status affects erectile function by regulating the expression of adenosine A2A and A2B receptors in rat penile corpus cavernosum. Thirty-six 8-week-old male Sprague-Dawley rats were randomly divided into six groups: sham-operated group (4w-sham, 8w-sham), castration group (4w-cast, 8w-cast) and androgen replacement group (4w-cast+T, 8w-cast+T). The rats in the androgen replacement groups were subcutaneously injected with testosterone propionate (3 mg/kg) every other day after castration. The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), the expression of A2A , A2B , AKT and eNOS and the concentrations of cAMP and cGMP in the corpus cavernosum were detected at the 4th and 8th weeks after the operation. The serum testosterone level and the ratio of ICPmax/MAP decreased significantly in the castration group as compared to other groups (p < 0.01). There was no significant difference in the expression of A2A receptor among groups, while the expression of A2B , AKT and eNOS and the concentrations of cAMP and cGMP in the castration group were significantly lower than in other groups (p < 0.01). Low androgen status inhibits the AKT/eNOS/cGMP signalling pathways and the production of cAMP in the corpus cavernosum of castrated rats by down-regulating the expression of A2B receptor, and results in decreased of ICPmax/MAP.


Assuntos
Androgênios/metabolismo , Disfunção Erétil/fisiopatologia , Pênis/metabolismo , Receptor A2A de Adenosina/metabolismo , Receptor A2B de Adenosina/metabolismo , Androgênios/sangue , Animais , Pressão Arterial/efeitos dos fármacos , Pressão Arterial/fisiologia , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Terapia de Reposição Hormonal/métodos , Humanos , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Orquiectomia/efeitos adversos , Ereção Peniana/efeitos dos fármacos , Ereção Peniana/fisiologia , Pênis/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Propionato de Testosterona/administração & dosagem
18.
Pharmacol Res Perspect ; 7(3): e00477, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31164986

RESUMO

Vandetanib and pazopanib are clinically available, multi-targeted inhibitors of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinases. Short-term VEGF receptor inhibition is associated with hypertension in 15%-60% of patients, which may limit the use of these anticancer therapies over the longer term. To evaluate the longer-term cardiovascular implications of treatment, we investigated the "on"-treatment (21 days) and "off"-treatment (10 days) effects following daily administration of vandetanib, pazopanib, or vehicle, in conscious rats. Cardiovascular variables were monitored in unrestrained Sprague-Dawley rats instrumented with radiotelemetric devices. In Study 1, rats were randomly assigned to receive either daily intraperitoneal injections of vehicle (volume 0.5 mL; n = 5) or vandetanib 25 mg/kg/day (volume 0.5 mL; n = 6). In Study 2, rats received either vehicle (volume 0.5 mL; n = 4) or pazopanib 30 mg/kg/day (volume 0.5 mL; n = 7), dosed once every 24 hours for 21 days. All solutions were in 2% Tween, 5% propylene glycol in 0.9% saline solution. Vandetanib caused sustained increases in mean arterial pressure (MAP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) compared to baseline and vehicle. Vandetanib also significantly altered the circadian cycling of MAP, SBP, and DBP. Elevations in SBP were detectable 162 hours after the last dose of vandetanib. Pazopanib also caused increases in MAP, SBP, and DBP. However, compared to vandetanib, these increases were of slower onset and a smaller magnitude. These data suggest that the cardiovascular consequences of vandetanib and pazopanib treatment are sustained, even after prolonged cessation of drug treatment.


Assuntos
Hipertensão/induzido quimicamente , Piperidinas/efeitos adversos , Pirimidinas/efeitos adversos , Quinazolinas/efeitos adversos , Sulfonamidas/efeitos adversos , Animais , Pressão Arterial/efeitos dos fármacos , Modelos Animais de Doenças , Esquema de Medicação , Humanos , Masculino , Piperidinas/administração & dosagem , Pirimidinas/administração & dosagem , Quinazolinas/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sulfonamidas/administração & dosagem
19.
J Bras Pneumol ; 45(3): e20170164, 2019 May 30.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31166552

RESUMO

OBJECTIVE: To evaluate the pulmonary alterations of animals with Hepatopulmonary Syndrome (HPS) submitted to Biliary Duct Ligature (BDL), as well as the antioxidant effect of Melatonin (MEL). METHODS: Sixteen male Wistar rats, divided into four Sham groups: BDL group, Sham + MEL group and BDL + MEL. The pulmonary and hepatic histology, lipoperoxidation and antioxidant activity of lung tissue, alveolar-arterial O2 difference and lung / body weight ratio (%) were evaluated. RESULTS: When comparing the groups, could be observed an increase of vasodilation and pulmonary fibrosis in the BDL group and the reduction of this in relation to the BDL + MEL group. It was also observed significant changes in the activity of catalase, ApCO2, ApO2 in the LBD group when compared to the other groups. CONCLUSION: The use of MEL has been shown to be effective in reducing vasodilation, fibrosis levels and oxidative stress as well as gas exchange in an experimental HPS model.


Assuntos
Antioxidantes/farmacologia , Síndrome Hepatopulmonar/tratamento farmacológico , Pulmão/efeitos dos fármacos , Melatonina/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Ductos Biliares/cirurgia , Gasometria , Catalase/análise , Modelos Animais de Doenças , Glutationa Transferase/análise , Síndrome Hepatopulmonar/patologia , Síndrome Hepatopulmonar/fisiopatologia , Ligadura , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/fisiopatologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Reprodutibilidade dos Testes , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Resultado do Tratamento
20.
Int. j. morphol ; 37(2): 739-743, June 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1002287

RESUMO

La preeclampsia (PE) es un trastorno hipertensivo inducido por el embarazo donde se reduce la presión de la perfusión uterina. Investigaciones avalan el uso de dosis baja de aspirina (DBAAS) y su utilidad en la prevención de PE en gestantes con factores de riesgo. Sus beneficios en modelos animales sometidos a esta reduccción no están determinados. El objetivo de la investigación fue analizar la presión arterial sistémica y los hallazgos morfológicos a nivel renal en fetos de ratas con reducción de la presión de perfusión uterina (RPPU) expuestas a DBAAS en comparación a las no expuestas. Se conformaron cuatro grupos de ratas hembras preñadas Sprague Dawley (n=5). A los 14,5 días post-concepción (dpc), vía quirúrgica se indujo RPPU, ligando arterias uterinas, conformándose el grupo RPPU y el grupo RPPU+DBAAS al que se le administró 5 mg/kg/día de aspirina vía oral. El grupo control lo conformaron las no operadas y el grupo DBAAS se le administró aspirina en igual dosis desde el 14,5 dpc. A los 18,5 dpc, previo a la eutansia se midió la presión arterial sistémica con pletismógrafo caudal Insight v2.11 y se extrajeron los fetos. Se midió la longitud céfalo-caudal (LCC), se procesaron y tiñeron con hematoxilina-eosina, describiéndose cortes histológicos transversales a nivel renal. Se determinó que en la presión arterial media, hubo diferencias significativas entre el grupo RPPU y RPPU+DBAAS (p<0,05). El tamaño de los fetos fue menor en el grupo RPPU (p<0,0001), donde 1 feto presentó hernia umbilical congénita. La cuantificación de vesículas renales también fue menor (p<0,005). En conclusión, la administración de DBAAS disminuye los efectos inducidos por la RPPU en cuanto al tamaño fetal, morfología renal y malformaciones congénitas como hernia umbilical. En cuanto a la presión arterial sistémica, tendría efectos sólo en presión arterial media.


Preeclampsia (PE) is a hypertensive disorder induced by pregnancy where there is a reduction in the uterine perfusion pressure. Research supports the use of low dose aspirin (LDAAS) and its usefulness in the prevention of PE in pregnant women with risk factors. Their benefits in animal models subject to RUPP are not determined. The objective of the investigation was to analyze the systemic blood pressure and the morphological findings at renal level in fetuses of rats with reduction of uterine perfusion pressure (RUPP) exposed to LDAAS compared to those not exposed. Four groups of pregnant female rats Sprague Dawley (n=5) were formed. At 14.5 days post-conception (dpc), surgical RUPP was induced, ligating uterine arteries, with the RUPP group and RUPP+LDAAS group being given 5 mg/kg/day of aspirin orally. The control group was made up of those not operated and the LDAAS group was administered aspirin in the same dose from 14.5 dpc. A 18.5 dpc, prior to euthanasia systemic blood pressure was measured with flow plethysmograph Insight v2.11 and fetuses were extracted. The cephalo-caudal length (CCL) was measured, processed and stained with hematoxylin-eosin, describing transverse histological sections at the kidney level. It was determined that in the mean arterial pressure, there were significant differences between the group RUPP and RUPP+LDAAS (p <0.05). The size of the fetuses was lower in the RUPP group (p <0.0001), where one fetus presented congenital umbilical hernia. The quantification of renal vesicles was also lower (p <0.005). In conclusion, the administration of LDAAS decreases the effects induced by RUPP in terms of fetal size, renal morphology and congenital malformations such as umbilical hernia. Regarding the systemic blood pressure, effects would only mean arterial pressure.


Assuntos
Animais , Feminino , Gravidez , Ratos , Pressão Sanguínea/efeitos dos fármacos , Aspirina/administração & dosagem , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Perfusão , Fluxo Sanguíneo Regional , Útero/irrigação sanguínea , Aspirina/farmacologia , Estudos Prospectivos , Estudos Longitudinais , Ratos Sprague-Dawley , Feto , Pressão Arterial/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA