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Type: Artigo de periódico
Title: Functional Antagonism Of β-adrenoceptor Subtypes In The Catecholamine-induced Automatism In Rat Myocardium
Author: Boer D.C.
Bassani J.W.M.
Bassani R.A.
Abstract: Background and Purpose Myocardial automatism and arrhythmias may ensue during strong sympathetic stimulation. We sought to investigate the relevant types of adrenoceptor, as well as the role of phosphodiesterase (PDE) activity, in the production of catecholaminergic automatism in atrial and ventricular rat myocardium. Experimental Approach The effects of adrenoceptor agonists on the rate of spontaneous contractions (automatic response) and the amplitude of electrically evoked contractions (inotropic response) were determined in left atria and ventricular myocytes isolated from Wistar rats. KEY RESULTS Catecholaminergic automatism was Ca 2+-dependent, as it required a functional sarcoplasmic reticulum to be exhibited. Although both α- and β-adrenoceptor activation caused inotropic stimulation, only β 1-adrenoceptors seemed to mediate the induction of spontaneous activity. Catecholaminergic automatism was enhanced and suppressed by β 2-adrenoceptor blockade and stimulation respectively. Inhibition of either PDE3 or PDE4 (by milrinone and rolipram, respectively) potentiated the automatic response of myocytes to catecholamines. However, only rolipram abolished the attenuation of automatism produced by β 2-adrenoceptor stimulation. Conclusions and Implications α- and β 2-adrenoceptors do not seem to be involved in the mediation of catecholaminergic stimulation of spontaneous activity in atrial and ventricular myocardium. However, a functional antagonism of β 1- and β 2-adrenoceptor activation was identified, the former mediating catecholaminergic myocardial automatism and the latter attenuating this effect. Results suggest that hydrolysis of cAMP by PDE4 is involved in the protective effect mediated by β 2-adrenoceptor stimulation. © 2011 The British Pharmacological Society.
Rights: fechado
Identifier DOI: 10.1111/j.1476-5381.2010.01121.x
Date Issue: 2011
Appears in Collections:Unicamp - Artigos e Outros Documentos

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