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1.
Cell Physiol Biochem ; 53(4): 587-605, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31535830

RESUMO

BACKGROUND/AIMS: To investigate the role of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in renal ischemia/reperfusion-induced (I/R) cardiac inflammatoryprofile. METHODS: Left kidney ischemia was induced in male C57BL/6 mice for 60 min, followed by reperfusion for 12 days, and treatment with or without atenolol, losartan, or enalapril. The expression of vimentin in kidney and atrial natriuretic factor (ANF) in the heart has been investigated by RT-PCR. In cardiac tissue, levels of ß1-adrenoreceptors, adenylyl cyclase, cyclic AMP-dependent protein kinase (PKA), noradrenaline, adrenaline (components of SNS), type 1 angiotensin II receptors (AT1R), angiotensinogen/Ang II and renin (components of RAS) have been measured by Western blotting and HPLC analysis. A panel of cytokines - tumour necrosis factor (TNF-α), interleukin IL-6, and interferon gamma (IFN-γ) - was selected as cardiac inflammatory markers. RESULTS: Renal vimentin mRNA levels increased by >10 times in I/R mice, indicative of kidney injury. ANF, a marker of cardiac lesion, increased after renal I/R, the values being restored to the level of Sham group after atenolol or enalapril treatment. The cardiac inflammatory profile was confirmed by the marked increase in the levels of mRNAs of TNF-α, IL-6, and IFN-γ. Atenolol and losartan reversed the upregulation of TNF-α expression, whereas enalapril restored IL-6 levels to Sham levels; both atenolol and enalapril normalized IFN-γ levels. I/R mice showed upregulation of ß1-adrenoreceptors, adenylyl cyclase, PKA and noradrenaline. Renal I/R increased cardiac levels of AT1R, which decreased after losartan or enalapril treatment. Renin expression also increased, with the upregulation returning to Sham levels after treatment with SNS and RAS blockers. Angiotensinogen/Ang II levels in heart were unaffected by renal I/R, but they were significantly decreased after treatment with losartan and enalapril, whereas increase in renin levels decreased. CONCLUSION: Renal I/R-induced cardiac inflammatory events provoked by the simultaneous upregulation of SNS and RAS in the heart, possibly underpin the mechanism involved in the development of cardiorenal syndrome.


Assuntos
Rim/metabolismo , Miocárdio/metabolismo , Sistema Renina-Angiotensina , Sistema Nervoso Simpático/metabolismo , Animais , Atenolol/farmacologia , Atenolol/uso terapêutico , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Catecolaminas/metabolismo , Enalapril/farmacologia , Enalapril/uso terapêutico , Interleucina-6/metabolismo , Losartan/farmacologia , Losartan/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 1/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Sistema Nervoso Simpático/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Vimentina/genética , Vimentina/metabolismo
2.
J Pharm Pharmacol ; 71(10): 1576-1583, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31347707

RESUMO

OBJECTIVES: Paraoxonase-1 (PON1) enzyme is related to high-density lipoprotein (HDL), which is calcium dependent. It has essential roles such as protecting LDL against oxidation and detoxification of highly toxic substances. It is a significant risk to reduce the levels of this enzyme in patients with diabetes mellitus, cardiovascular diseases, hyperthyroidism and chronic renal failure. METHODS: Here, it was reported that the purification of human serum PON1 using straightforward methods and determination of the interactions between some antihypertension drugs and the enzyme. KEY FINDING: It was found that these drugs exhibit potential inhibitor properties for human serum PON1 with IC50 values in the range of 131.40-369.40 µm and Ki values in the range of 56.24 ± 6.75-286.74 ± 28.28 µm. These drugs showed different inhibition mechanisms. It was determined that midodrine and nadolol were exhibited competitive inhibition, but atenolol and pindolol were exhibited non-competitive inhibition. CONCLUSION: Usage of these drugs would be hazardous in some cases.


Assuntos
Anti-Hipertensivos/farmacologia , Arildialquilfosfatase/sangue , Aterosclerose/sangue , Aterosclerose/tratamento farmacológico , Atenolol/farmacologia , Humanos , Lipoproteínas HDL/sangue , Midodrina/farmacologia , Nadolol/farmacologia , Pindolol/farmacologia
3.
Chemosphere ; 236: 124318, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31319310

RESUMO

The present paper deals with the atenolol (ATL) degradation by advanced anodic oxidation using a boron-doped diamond anode supported on niobium (Nb/BDD). Cyclic voltammetry performed on this electrode revealed that it presents a high quality (diamond-sp3/sp2-carbon ratio), high potential for OER and that ATL can be oxidized directly and/or indirectly by the electrogenerated oxidants, such as hydroxyl radicals, persulfate ions and sulfate radicals. Electrolysis experiments demonstrated that ATL degradation and mineralization follow a mixed (first and zero) order kinetics depending on the applied current density. At high applied current densities, the amount of OH radicals is very high and the overall reaction is limited by the transport of ATL (pseudo first-order kinetics) whereas for low applied current densities, the rate of OH radicals generation at the anode is slower than the rate of arrival of ATL molecules (pseudo-zero order kinetics). Estimated values of kzero and kfirst based on the assumption of pseudo-zero or pseudo-first order kinetics were carried oud as a function of the supporting electrolyte concentration, indicating that both parameters increased with its concentration due the higher production of sulfate reactive species that play an important role in degradation. Finally, MCE increased with the decrease of current density, due to the lower amount of OH present in solution, since this species could be rapidly wasted in parasitic reactions; and the increase of sulfate concentration due to the more efficient production of persulfate.


Assuntos
Atenolol/uso terapêutico , Eletrólise/métodos , Nióbio/química , Atenolol/farmacologia , Eletrodos
4.
Acta Cir Bras ; 34(5): e201900505, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166461

RESUMO

PURPOSE: To evaluate the cardioprotective response of the pharmacological modulation of ß-adrenergic receptors (ß-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. METHODS: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with ß-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with ß-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. RESULTS: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of ß-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of ß-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). CONCLUSION: The pharmacological modulation of ß-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Agonistas Adrenérgicos beta/farmacologia , Atenolol/farmacologia , Cardiotônicos/farmacologia , Isoproterenol/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Receptores Adrenérgicos beta/efeitos dos fármacos , Animais , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Creatina Quinase Forma MB/sangue , Testes de Função Cardíaca , Masculino , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Ratos Endogâmicos SHR , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
5.
Eur J Pharm Sci ; 131: 93-98, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30753892

RESUMO

ß-blockers show variable efficacy as antihypertensives. Herein, we evaluated plasma miRNAs as biomarkers for defining antihypertensive response to ß-blockers. Expression of 22 ß-blocker pharmacodynamics-related miRNAs was assessed in baseline plasma samples from 30 responders and 30 non-responders to metoprolol from the PEAR-2 study (Discovery). Logistic regression was performed to identify miRNAs significantly associated with metoprolol response. Those miRNAs were profiled in baseline plasma samples from 25 responders and 25 non-responders to atenolol from the PEAR study (validation). In discovery, miR-101, miR-27a, miR-22, miR-19a, and let-7e were significantly associated with metoprolol response (P = 0.01, 0.017, 0.025, 0.025, and 0.04, respectively). In validation, miR-19a was significantly associated with atenolol response (P = 0.038). Meta-analysis between PEAR-2 and PEAR revealed significant association between miR-19a (P = 0.004), miR-101 (P = 0.006), and let-7e (P = 0.012) and ß-blocker response. Hence, miR-19a, miR-101, and let-7e, which regulate ß1-adrenergic receptor and other ß-blocker pharmacodynamics-related genes, may be biomarkers for antihypertensive response to ß-blockers.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Anti-Hipertensivos/farmacologia , Atenolol/farmacologia , Metoprolol/farmacologia , MicroRNAs/sangue , Adulto , Feminino , Humanos , Hipertensão/sangue , Hipertensão/genética , Masculino , Pessoa de Meia-Idade
6.
Am J Vet Res ; 80(3): 270-274, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30801219

RESUMO

OBJECTIVE To test the hypothesis that once-daily oral administration of atenolol would attenuate the heart rate response to isoproterenol for 24 hours. ANIMALS 20 healthy dogs. PROCEDURES A double-blind randomized placebo-controlled crossover study was conducted. Dogs were assigned to receive atenolol (1 mg/kg, PO, q 24 h) or a placebo for 5 to 7 days. After a washout period of 7 days, dogs then received the other treatment. Heart rate at rest (HRr) and heart rate induced by administration of isoproterenol (HRi) as a constant rate infusion (0.2 µg/kg/min for 5 to 7 minutes) were obtained by use of ECG 0, 0.25, 3, 6, 12, 18, and 24 hours after administration of the final dose of atenolol or the placebo. A mixed-model ANOVA was used to evaluate effects of treatment, time after drug or placebo administration, treatment-by-time interaction, period, and sequence on HRr and HRi. RESULTS Effects of sequence or period were not detected. There was a significant effect of treatment and the treatment-by-time interaction on HRi. Atenolol significantly attenuated HRi for 24 hours but did so maximally at 3 hours (least squares mean ± SE, 146 ± 5 beats/min and 208 ± 5 beats/min for atenolol and placebo, respectively). The effect at 24 hours was small (193 ± 5 beats/min and 206 ± 5 beats/min for atenolol and placebo, respectively). Atenolol had a small but significant effect on HRr. CONCLUSIONS AND CLINICAL RELEVANCE This study of healthy dogs receiving atenolol supported a recommendation for a dosing interval < 24 hours.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Agonistas Adrenérgicos beta , Atenolol/farmacologia , Cães , Isoproterenol/antagonistas & inibidores , Administração Oral , Animais , Pressão Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Distribuição Aleatória
7.
Drug Res (Stuttg) ; 69(2): 83-92, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29996172

RESUMO

There is a growing global interest in hypertension due to its associated complications including renal dysfunction in patients. The thyroid system reportedly regulates renal function in both animal and human. The present study investigated the therapeutic efficacy of taurine on renal and thyroid dysfunctions in hypertensive rats. Hypertension was induced by oral administration of nitric oxide synthase inhibitor, N-nitro L-arginine-methyl-ester (L-NAME), at 40 mg/kg body weight to the male Wistar rats for 14 consecutive days. The hypertensive rats were subsequently treated with either taurine (100 and 200 mg/kg) or reference drug atenolol (10 mg/kg) for another 14 consecutive days. Hypertensive rats showed renal damage evidenced by elevated plasma creatinine and urea levels when compared with normotensive control rats. Furthermore, L-NAME-induced hypertensive rats showed decreased circulatory concentrations of thyroid stimulating hormone, thyroxine, triiodothyronine and the ratio of triiodothyronine to thyroxine. The marked decrease in the renal antioxidant enzyme activities and nitric oxide level was accompanied by significant increase in myeloperoxidase activity and biomarkers of oxidative stress in hypertensive rats. Histological examination of kidneys from hypertensive rats revealed congestion of blood vessels, hemorrhagic lesion and disorganized glomerular structure. However, treatment with taurine or atenolol significantly reversed the suppression of thyroid function, ameliorated renal oxidative stress and histopathological lesions in L-NAME-induced hypertensive rats. Taurine may be a useful chemotherapeutic supplement in enhancing renal and thyroid functions in hypertensive patients.


Assuntos
Hipertensão/complicações , Insuficiência Renal/prevenção & controle , Taurina/administração & dosagem , Glândula Tireoide/fisiopatologia , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Atenolol/farmacologia , Atenolol/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Suplementos Nutricionais , Modelos Animais de Doenças , Humanos , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/patologia , Masculino , NG-Nitroarginina Metil Éster/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Insuficiência Renal/etiologia , Insuficiência Renal/patologia , Glândula Tireoide/efeitos dos fármacos
8.
J Clin Hypertens (Greenwich) ; 20(10): 1464-1472, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30289609

RESUMO

A quantitative survey was completed by 103 primary care physicians (PCPs) and 59 cardiologists who regularly prescribed ß-blockers to assess knowledge and use of this heterogeneous drug class for hypertension. More cardiologists than PCPs chose ß-blockers as initial antihypertensive therapy (30% vs 17%, P < 0.01). Metoprolol and carvedilol were the most commonly prescribed ß-blockers. Cardiologists rated "impact on energy" and "arterial vasodilation" as more important than PCPs (P < 0.05/<0.01, respectively). Awareness of vasodilation was greater for carvedilol (52%) than nebivolol (31%). Association between ß-blockers and clinical variables included nebivolol with ß1 -selectivity, nebivolol and carvedilol with vasodilation and efficacy in older patients and African Americans, metoprolol with heart rate reduction, and atenolol and metoprolol with weight gain and hyperglycemia. Physicians preferred prescribing ß-blockers with lower risk of incident diabetes. Clinical practice guidelines influenced physician prescribing more than formularies or performance metrics. This survey captures physicians' perceptions/use of various ß-blockers and clinically relevant knowledge gaps.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Cardiologistas/estatística & dados numéricos , Hipertensão/tratamento farmacológico , Médicos de Atenção Primária/estatística & dados numéricos , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Afro-Americanos/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Atenolol/efeitos adversos , Atenolol/farmacologia , Cardiologistas/psicologia , Carvedilol/efeitos adversos , Carvedilol/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/epidemiologia , Hipertensão/mortalidade , Metoprolol/efeitos adversos , Metoprolol/farmacologia , Nebivolol/efeitos adversos , Nebivolol/farmacologia , Percepção , Médicos de Atenção Primária/psicologia , Guias de Prática Clínica como Assunto , Inquéritos e Questionários , Vasodilatação/efeitos dos fármacos
9.
J Clin Hypertens (Greenwich) ; 20(11): 1603-1609, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30267456

RESUMO

Beta-blockers are one of the most commonly prescribed classes of antihypertensive medications during pregnancy. Previous studies reported an association between beta-blocker exposure and intrauterine growth restriction. Whether some beta-blocker subtypes may be associated with higher risk is not known. This is a retrospective cohort study of pregnant women exposed to beta-blockers in the Kaiser Permanente Southern California Region between 2003 and 2014. Logistic regression models were used to evaluate association between exposure to different beta-blocker agents and risk of low fetal birth weights. In a cohort of 379 238 singleton pregnancies, 4847 (1.3%) were exposed to beta-blockers. The four most commonly prescribed beta-blockers were labetalol (n = 3357), atenolol (n = 638), propranolol (n = 489), and metoprolol (n = 324). Mean birth weight and % low birth weight (<2500 g) were 2926 ± 841 g and 24.4% for labetalol, 3058 ± 748 g and 18.0% for atenolol, 3163 ± 702 g and 13.3% for metoprolol, 3286 ± 651 g and 7.6% for propranolol, and 3353 ± 554 g and 5.2% for non-exposed controls. Exposure to atenolol and labetalol were associated with increased risks of infant born small for gestational age (SGA) (atenolol: adjusted OR 2.4, 95% CI: 1.7-3.3; labetalol: adjusted OR 2.9, 95% CI: 2.6-3.2). Risk of SGA associated with metoprolol or propranolol exposure was not significantly different from the non-exposed group (metoprolol: adjusted OR 1.5, 95% CI: 0.9-2.3; propranolol: adjusted OR 1.3, 95% CI: 0.9-1.9). Association between beta-blocker exposure and SGA does not appear to be a class effect. Variations in pharmacodynamics and confounding by indication may explain these findings.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Anti-Hipertensivos/farmacologia , Peso ao Nascer/efeitos dos fármacos , Retardo do Crescimento Fetal/induzido quimicamente , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Atenolol/efeitos adversos , Atenolol/farmacologia , Atenolol/uso terapêutico , California/epidemiologia , Feminino , Retardo do Crescimento Fetal/epidemiologia , Retardo do Crescimento Fetal/etnologia , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Labetalol/efeitos adversos , Labetalol/farmacologia , Labetalol/uso terapêutico , Masculino , Metoprolol/efeitos adversos , Metoprolol/farmacologia , Metoprolol/uso terapêutico , Gravidez , Prevalência , Propranolol/efeitos adversos , Propranolol/farmacologia , Propranolol/uso terapêutico , Estudos Retrospectivos
10.
Auton Neurosci ; 214: 1-8, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30177218

RESUMO

Improved understanding of how depression and social isolation interact to increase cardiac morbidity and mortality will improve public health. This experiment evaluated the effect of pharmacological autonomic blockade on cardiac and behavioral reactivity following social isolation in prairie voles. Experiment 1 validated the dose and time course of pharmacological autonomic antagonism of peripheral ß-adrenergic (atenolol) and muscarinic cholinergic receptors (atropine methyl nitrate), and Experiment 2 used a novel protocol to investigate behavioral responses in the tail suspension test during pharmacological autonomic blockade as a function of social isolation (vs. paired control). Prairie voles isolated for 4 weeks (vs. paired) displayed significantly elevated heart rate and reduced heart rate variability. Autonomic receptor antagonism by atenolol led to exaggerated reductions in heart rate and standard deviation of normal-to-normal intervals, and lower amplitude of respiratory sinus arrhythmia in the isolated group (vs. paired). Administration of atropine led to an attenuated increase in heart rate in the isolated group (vs. paired), and similar near-zero levels of respiratory sinus arrhythmia amplitude in both groups. During the tail suspension test, isolated animals (vs. paired) displayed significantly greater immobility. In paired animals, atenolol administration did not influence immobility; atropine administration increased the duration of immobility (vs. vehicle). In isolated animals, atenolol administration increased the duration of immobility; atropine did not influence immobility duration (vs. vehicle). The current study contributes to our understanding of differential effects of social isolation and autonomic imbalance on cardiac and behavioral reactivity.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Comportamento Animal/fisiologia , Frequência Cardíaca/fisiologia , Isolamento Social/psicologia , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Análise de Variância , Animais , Arvicolinae , Atenolol/farmacologia , Atropina/farmacologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Depressão/etiologia , Eletrocardiografia , Frequência Cardíaca/efeitos dos fármacos , Elevação dos Membros Posteriores , Masculino , Antagonistas Muscarínicos/farmacologia , Telemetria
11.
Environ Toxicol Pharmacol ; 63: 1-5, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30107356

RESUMO

Hypertension, a chronic non-transmissible multifactorial condition, it is highly frequent in Brazil, affecting about 32.5% of the population over 25 years of age. It is characterized by the sustained increase in systolic and diastolic blood pressure levels above 140 mmHg and 90 mmHg, respectively. It is the major aggravating factor in cardiovascular complications and the appearance of other comorbidities. Aiming to promote greater adherence to treatment and improve the population's access to basic medicament, in 2004 the Federal Government created the Programa Farmácia Popular do Brasil (PFPB); partnership with private institutions that provides the population with medicament to control hypertension, free of charge or subsidized at up to 90% of the value. The PFPB distributes the anti-hypertensives atenolol, captopril, enalapril, hydrochlorothiazide, losartan and propranolol. In this way, this work aims to evaluate the genotoxic potential of antihypertensives in human lymphocytes and macrophages, since they are widely used drugs and with few studies about their genotoxicological safety. The tests were developed from cell cultures treated with five different antihypertensive concentrations, all based on plasma peaks, evaluating cell viability, DNA damage index and DNA double strand breakdown. The results show that, as the concentration of captopril and enalapril maleate increased, cell viability decreased. In addition, a DNA damage was observed with the use Captopril and Enalapril in the higher concentrations. Hydrochlorothiazide also caused DNA damage in the five doses tested. Regarding the breaking of double strands of DNA, all the compounds showed increased ruptures. This decrease in dsDNA is dose dependent for all compounds tested. The set of results shows that the use although frequent still requires care and greater knowledge. In general, the antihypertensive drugs that proved to be safer in relation to the genetic damage tested were Losartan and Propranolol.


Assuntos
Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológico , Linfócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Anti-Hipertensivos/farmacologia , Atenolol/efeitos adversos , Atenolol/farmacologia , Brasil , Captopril/efeitos adversos , Captopril/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dano ao DNA , Relação Dose-Resposta a Droga , Enalapril/efeitos adversos , Enalapril/farmacologia , Programas Governamentais , Humanos , Hidroclorotiazida/efeitos adversos , Hidroclorotiazida/farmacologia , Losartan/efeitos adversos , Losartan/farmacologia , Linfócitos/citologia , Macrófagos/citologia , Masculino , Testes de Mutagenicidade , Avaliação de Programas e Projetos de Saúde , Propranolol/efeitos adversos , Propranolol/farmacologia
12.
Pharmacol Rep ; 70(5): 917-929, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30099298

RESUMO

BACKGROUND: To evaluate the protective effect of nebivolol against kidney damage and elucidate the underlying mechanism in a two-kidney, one-clip (2K1C) rat model. METHODS: 2K1C rats were obtained by clipping left renal artery of male Wistar rats and were considered hypertensive when systolic blood pressure (SBP) was ≥160mmHg 4 weeks after surgery. The 2K1C hypertensive rats were divided into untreated, nebivolol (10mg/kg, ig), and atenolol (80mg/kg, ig) treatment groups. The treatments lasted for 8 weeks. SBP, kidney structure and function, plasma and kidney angiotensin (Ang) II, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and the oxidant status were examined. Kidney protein expression of NADPH oxidase (Nox) isoforms and its subunit p22phox, nitric oxide synthase (NOS) isoforms, protein arginine N-methyltransferase (PRMT) 1, and dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 was tested by western blotting. RESULTS: Nebivolol and atenolol exerted similar hypotensive effects. However, atenolol had little effect while nebivolol significantly ameliorated the functional decline and structural damage in the kidney, especially in non-clipped kidney (NCK), which was associated with the reduction of Ang II in NCK. Moreover, nebivolol inhibited the NCK production of reactive oxygen species (ROS) by decreasing Nox2, Nox4, and p22phox expression. Further, nebivolol reduced the plasma and kidney ADMA levels by increasing DDAH2 expression and decreasing PRMT1 expression. Nebivolol also increased the NCK NO level by ameliorating the expression of kidney NOS isoforms. CONCLUSIONS: Our results demonstrated that long-term treatment with nebivolol had renoprotective effect in 2K1C rats partly via regulation of kidney ROS-ADMA-NO pathway.


Assuntos
Amidoidrolases/biossíntese , Hipertensão Renovascular/tratamento farmacológico , Nebivolol/farmacologia , Nebivolol/uso terapêutico , Óxido Nítrico/metabolismo , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Angiotensina II/sangue , Angiotensina II/metabolismo , Animais , Arginina/análogos & derivados , Arginina/sangue , Arginina/metabolismo , Atenolol/farmacologia , Pressão Sanguínea/fisiologia , Hipertensão Renovascular/metabolismo , Rim/efeitos dos fármacos , Rim/lesões , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Masculino , NADPH Oxidases/biossíntese , Óxido Nítrico/sangue , Óxido Nítrico Sintase/biossíntese , Substâncias Protetoras/uso terapêutico , Proteína-Arginina N-Metiltransferases/biossíntese , Ratos , Transdução de Sinais/efeitos dos fármacos
13.
Emerg Med J ; 35(9): 559-563, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29921621

RESUMO

OBJECTIVES: Beta blockers (ß-blockers) remain a standard therapy in the early treatment of acute coronary syndromes. However, ß-blocker therapy in patients with cocaine-associated chest pain (CACP) continues to be an area of debate due to the potential risk of unopposed α-adrenergic stimulation and coronary vasospasm. Therefore, we performed a systematic review and meta-analysis of available studies to compare outcomes of ß-blocker versus no ß-blocker use among patients with CACP. METHODS: We searched the MEDLINE and EMBASE databases through September 2016 using the keywords 'beta blocker', 'cocaine' and commonly used ß-blockers ('atenolol', 'bisoprolol', 'carvedilol', 'esmolol', 'metoprolol' and 'propranolol') to identify studies evaluating ß-blocker use among patients with CACP. We specifically focused on studies comparing outcomes between ß-blocker versus no ß-blocker usage in patients with CACP. Studies without a comparison between ß-blocker and no ß-blocker use were excluded. Outcomes of interest included non-fatal myocardial infarction (MI) and all-cause mortality. Quantitative data synthesis was performed using a random-effects model and heterogeneity was assessed using Q and I2statistics. RESULTS: A total of five studies evaluating 1794 subjects were included. Overall, there was no significant difference on MI in patients with CACP on ß-blocker versus no ß-blocker (OR 1.36, 95% CI 0.68 to 2.75; p=0.39). Similarly, there was no significant difference in all-cause mortality in patients on ß-blocker versus no ß-blocker (OR 0.68, 95% CI 0.26 to 1.79; p=0.43). CONCLUSIONS: In patients presenting with acute chest pain and underlying cocaine, ß-blocker use does not appear to be associated with an increased risk of MI or all-cause mortality.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Antagonistas Adrenérgicos beta/farmacologia , Cocaína/efeitos adversos , Síndrome Coronariana Aguda/etiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Atenolol/farmacologia , Atenolol/uso terapêutico , Bisoprolol/farmacologia , Bisoprolol/uso terapêutico , Carvedilol/farmacologia , Carvedilol/uso terapêutico , Humanos , Metoprolol/farmacologia , Metoprolol/uso terapêutico , Propanolaminas/farmacologia , Propanolaminas/uso terapêutico , Propranolol/farmacologia , Propranolol/uso terapêutico
14.
Chemosphere ; 207: 174-182, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29793029

RESUMO

Atenolol (ATL) has been widely detected in wastewater and aquatic environment. Although satisfactory removal of ATL from wastewater could be achieved, the mineralization ratio is usually low, which may result in the accumulation of its transformation products in the effluent and cause additional ecological risk to the environment. The aim of this study is to explore the effectiveness of heat activated persulfate (PS) in the removal of ATL from wastewater. Influencing factors including temperature, PS dosage, solution pH, existence of NO3-, Cl-, HCO3- and Suwannee river fulvic acid (SRFA) were examined. Complete removal of ATL was achieved within 40 min at pH 7.0 and 70 °C by using 0.5 mM PS. Inhibitive effects of HCO3- and FA had been observed on ATL oxidation, which was increased with the increase of their concentration. Sulfate radical (SO4-) was determined as the main reactive species by quenching experiment. Eight intermediates produced in ATL degradation were identified, and four degradation pathways were proposed based on the analysis of mass spectrum and frontier electron densities. The distribution of major intermediates was influenced by reaction temperature. Hydroxylation intermediates and deamidation intermediate were the most prominent at 50 °C and 60 °C, respectively. All intermediates were completely degraded in 40 min except P134 at 70 °C. Effective removal of TOC (74.12%) was achieved with 0.5 mM PS, pH 7.0 and 70 °C after 240 min. The results proved that heat activation of PS is a promising method to remove organic pollutants in wastewater.


Assuntos
Atenolol/uso terapêutico , Sulfetos/química , Poluentes Químicos da Água/química , Atenolol/farmacologia , Temperatura Alta , Cinética , Oxirredução , Poluentes Químicos da Água/análise
15.
Cardiovasc Ther ; 36(4): e12434, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29752864

RESUMO

AIM: To examine the interference of ß-blockers with the chemokine stromal cell-derived factor-1 (SDF-1) found in cell homing receptors, C-X-C chemokine receptor type 4 (CXCR-4) and CXCR-7, and regulatory proteins of homing pathways, we administered atenolol, carvedilol, metoprolol, and propranolol for 30 days using an orogastric tube to hypertensive rats. METHOD: We collected blood samples before and after treatment and quantified the levels of SDF-1 with enzyme-linked immunosorbent assay (ELISA). On day 30 of treatment, the spontaneously hypertensive rats (SHR) were euthanized, and heart, liver, lung, and kidney tissues were biopsied. Proteins were isolated for determining the expression of CXCR-4, CXCR-7, GRK-2 (G protein-coupled receptors kinase 2), ß-arrestins (ß1-AR and ß2-AR), and nuclear factor kappa B (NFκB). RESULTS: We found that the study drugs modulated these proteins, and metoprolol and propranolol strongly affected the expression of ß1-AR (P = .0102) and ß2-AR (P = .0034). CONCLUSION: ß-blockers modulated tissue expression of the proteins and their interactions following 30 days of treatment. It evidences that this class of drugs can interfere with proteins of cell homing pathways.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Anti-Hipertensivos/farmacologia , Movimento Celular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Animais , Atenolol/farmacologia , Carbazóis/farmacologia , Carvedilol , Quimiocina CXCL12/sangue , Modelos Animais de Doenças , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Hipertensão/sangue , Hipertensão/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Metoprolol/farmacologia , Miocárdio/metabolismo , NF-kappa B/metabolismo , Propanolaminas/farmacologia , Propranolol/farmacologia , Ratos Endogâmicos SHR , Receptores CXCR/metabolismo , Receptores CXCR4/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta-Arrestina 1/metabolismo , beta-Arrestina 2/metabolismo
16.
J Mol Recognit ; 31(8): e2715, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29630759

RESUMO

In the present study, the interaction of human serum albumin (HSA) with some cardiovascular drugs (CARs) under physiological conditions was investigated via the fluorescence spectroscopic and Fourier transform infrared spectroscopy. The CAR included Captopril, Timolol, Propranolol, Atenolol, and Amiodarone. Cardiovascular drugs can effectively quench the endogenous fluorescence of HSA by static quenching mechanism. The fluorescence quenching of HSA is mainly caused by complex formation of HSA with CAR. The binding reaction of CAR with HSA can be concluded that hydrophobic and electrostatic interactions are the main binding forces in the CAR-HSA system. The results showed that CAR strongly quenched the intrinsic fluorescence of HSA through a static quenching procedure, and nonradiation energy transfer happened within molecules. Fourier transform infrared spectroscopy absorption studies showed that the secondary structure was changed according to the interaction of HSA and CAR. The binding reaction of CAR with HSA can be concluded that hydrophobic and electrostatic interactions are the main binding forces in the CAR-HSA system. The results obtained herein will be of biological significance in pharmacology and clinical medicines.


Assuntos
Fármacos Cardiovasculares/química , Ligação Proteica/efeitos dos fármacos , Albumina Sérica Humana/química , Amiodarona/química , Amiodarona/farmacologia , Atenolol/química , Atenolol/farmacologia , Captopril/química , Captopril/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Propranolol/química , Propranolol/farmacologia , Albumina Sérica Humana/efeitos dos fármacos , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Timolol/química , Timolol/farmacologia
17.
Int J Biol Macromol ; 107(Pt B): 2436-2449, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29101044

RESUMO

The main aim of the present study was to design pH-sensitive bionanocomposite hydrogel beads based on CMC and HNT-AT nanohybrid and evaluate whether prepared bionanocomposite beads have the potential to be used in drug delivery applications. Atenolol (AT), as a model drug, was incorporated into the lumen of HA nanotubes via the co-precipitation technique. HNT/AT nanohybrid and CMC/HNT-AT beads were characterized via XRD, SEM, TGA, and FT-IR techniques. Drug loading and encapsulation efficiency was found to be high for CMC/HNT3 beads. Moreover, the swelling and drug release properties of the prepared CMC/HA-AT beads were investigated, and showed a pH sensitive swelling behavior with maximum its content at pH 6.8. Also, it was found that the swelling ratio of CMC/HNT beads was lower than that of pristine CMC beads. Drug release behavior of CMC/HNT-AT bionanocomposite hydrogel beads were investigated. A more sustained and controlled drug releases were observed for CMC/HNT-AT beads.


Assuntos
Silicatos de Alumínio/química , Atenolol/química , Carboximetilcelulose Sódica/química , Sistemas de Liberação de Medicamentos , Silicatos de Alumínio/farmacologia , Atenolol/farmacologia , Carboximetilcelulose Sódica/farmacologia , Argila , Liberação Controlada de Fármacos , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Concentração de Íons de Hidrogênio , Nanocompostos/química , Nanocompostos/uso terapêutico
18.
Mol Cell Biochem ; 445(1-2): 99-103, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29248973

RESUMO

The present study is designed for the assessment of various pathological changes like immunoglobins, C-reactive protein, vitamin D, sodium, potassium, calcium in stress-induced hypertensive rats. Albino Wistar rats of sex male were grouped into six. Each group consists of six animals. Groups were Group I (normal control), Group II (disease control), Group III (amlodipine control), Group IV (atenolol control), Group V (amlodipine treatment), and Group VI (atenolol treatment). Group II, V, and VI animals exposed to regular stress by placing them in cages individually and giving foot electric shocks (1 mA, 50 ms duration with 0.5-1 min of intervals regulated randomly by a computer) along with forced swimming (30 min) in order to induce hypertension in rats. This stress was given two times daily (morning and evening) for regular 15 days. Induction of hypertension was confirmed by measuring the tail arterial pressure of blood and angiotensin II. For next 1 month, Group III and V animals are treated with amlodipine with 1 mg/kg, s.c. dose while Group IV and VI animals were given 10 mg/kg, s.c. the dose of atenolol once daily. At the end of the experimental work, blood collected, rats sacrificed, and serum separated. Serum sodium, potassium, immunoglobins, C-reactive protein, vitamin D, and calcium were measured by semi-auto-analyzer. Stress-induced hypertension in rats produced altered serum sodium, potassium, immunoglobins, C-reactive protein, vitamin D, and calcium level which is restored by atenolol. Administration of amlodipine in animals without hypertension shows alteration in the level of immunoglobins, calcium, vitamin D, and electrolytes.


Assuntos
Anlodipino/farmacologia , Anti-Hipertensivos/farmacologia , Atenolol/farmacologia , Proteína C-Reativa/metabolismo , Eletrólitos/sangue , Hipertensão/etiologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Estresse Fisiológico , Vitamina D/sangue , Angiotensina II/sangue , Animais , Cálcio/sangue , Feminino , Masculino , Potássio/sangue , Ratos Wistar , Sódio/sangue
19.
Rev Cardiovasc Med ; 19(3): 97-101, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31054558

RESUMO

Although ischemic heart disease is invariably associated with marked activation of sympathetic nervous system, elevated levels of circulating catecholamines and lethal ventricular arrhythmias, the mechanisms of arrhythmogenesis due to myocardial ischemia are not fully understood. Since catecholamines are known to produce stimulatory effects in the heart mainly by acting on ß1-adrenoceptors, this study was undertaken to test the involvement of these receptors in the development of arrhythmias due to myocardial infarction (MI) induced upon occluding the left coronary artery in rats for a period of 2 h. The animals were treated with or without atenolol (20 mg/kg; daily), a selective ß1-adrenoceptors blocker, for 14 days before inducing MI. No alterations in the number of MIinduced episodes and incidence or duration of different types of arrhythmias were observed. In fact, the incidence of trigemines and reversible ventricular fibrillation due to MI were significantly increased in the atenolol-treated animals. These observations support the view that the activation of ß;1-adrenoceptors may not be exclusively involved in the development of arrhythmias during the occurrence of ischemic heart disease and other mechanisms can underlie the electric instability of such damaged heart.


Assuntos
Frequência Cardíaca , Infarto do Miocárdio/complicações , Miocárdio/metabolismo , Miocárdio/patologia , Receptores Adrenérgicos beta 1/metabolismo , Taquicardia Ventricular/etiologia , Fibrilação Ventricular/etiologia , Complexos Ventriculares Prematuros/etiologia , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Animais , Atenolol/farmacologia , Modelos Animais de Doenças , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Ratos Sprague-Dawley , Transdução de Sinais , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/patologia , Taquicardia Ventricular/fisiopatologia , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/patologia , Fibrilação Ventricular/fisiopatologia , Complexos Ventriculares Prematuros/metabolismo , Complexos Ventriculares Prematuros/patologia , Complexos Ventriculares Prematuros/fisiopatologia
20.
Acta Cir Bras ; 33(12): 1061-1066, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30624511

RESUMO

PURPOSE: To investigate the role of atenolol in the gene expression of caspase 1 (Casp1) and Bcl2L1 on vascular endothelium of rat intestine after ischemia and reperfusion (IR). METHODS: Eighteen adult male Wistar rats were randomly divided into 3 groups (n=6): SG (Sham group): no clamping of the superior mesenteric artery; IRG: IR plus saline group: IRG+At: IR plus Atenolol group. Rats from IRG and IRG+At were subjected to 60 min of intestinal ischemia and 120 min of reperfusion. Atenolol (2mg/kg) or saline were injected in the femoral vein 5 min before ischemia, 5 min and 55 min after reperfusion. Thereafter, intestinal segments were appropriately removed and processed for Endothelial Cell Biology Rat RT2 Profiler PCR Array. RESULTS: the anti-apoptotic Bcl2L1 gene expression was significantly down-regulated (-1.10) in the IRG and significantly up-regulated in the IRG+At (+14.15). Meanwhile, despite Casp1 gene expression was upregulated in both groups, it was significantly higher in the IRG (+35.06) than the IRG+At (+6.68). CONCLUSIONS: Atenolol presents antiapoptotic effects on rat intestine subjected to IR partly by the up-regulation of the anti-apoptotic Bcl2L1 gene expression. Moreover, atenolol can mitigate the pro-apoptotic and pro-inflammatory effects of Casp1 gene on rat intestine after IR.


Assuntos
Atenolol/farmacologia , Caspase 1/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Intestino Delgado/irrigação sanguínea , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Proteína bcl-X/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspase 1/genética , Constrição , Citoproteção/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Endotélio Vascular , Masculino , Artéria Mesentérica Superior , Isquemia Mesentérica/prevenção & controle , Reação em Cadeia da Polimerase , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima/efeitos dos fármacos , Proteína bcl-X/genética
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