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|Type:||Artigo de periódico|
|Title:||Functional antagonism of beta-adrenoceptor subtypes in the catecholamine-induced automatism in rat myocardium|
|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 Ca2+-dependent, as it required a functional sarcoplasmic reticulum to be exhibited. Although both alpha- and beta-adrenoceptor activation caused inotropic stimulation, only beta(1)-adrenoceptors seemed to mediate the induction of spontaneous activity. Catecholaminergic automatism was enhanced and suppressed by beta(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 beta(2)-adrenoceptor stimulation. CONCLUSIONS AND IMPLICATIONS alpha- and beta(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 beta(1)- and beta(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 beta(2)-adrenoceptor stimulation.|
|Citation:||British Journal Of Pharmacology. Wiley-blackwell, v. 162, n. 6, n. 1314, n. 1325, 2011.|
|Appears in Collections:||Unicamp - Artigos e Outros Documentos|
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