Functional antagonism of ß-adrenoceptor subtypes in the catecholamine-induced automatism in rat myocardium
D. C. Boer, J. W. M. Bassani, R.A. Bassani
ARTIGO
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Agradecimentos: We are indebted to Ms. Elizângela S. Oliveira and Ms. Ana Carolina Fantin for the technical support. This study was partially supported by CNPq (Proc N. 300632/2005-3 and 141175/2002-8)
Abstract: 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...
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Abstract: 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. 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. Catecholaminergic automatism was Ca2+-dependent, as it required a functional sarcoplasmic reticulum to be exhibited. Although both a- and b-adrenoceptor activation caused inotropic stimulation, only b1-adrenoceptors seemed to mediate the induction of spontaneous activity. Catecholaminergic automatism was enhanced and suppressed by b2-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 b2-adrenoceptor stimulation. a- and b2-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 b1- and b2-adrenoceptor activation was identi?ed, 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 b2-adrenoceptor stimulation
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CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ
300632/2005-3 ; 141175/2002-8
Fechado
Functional antagonism of ß-adrenoceptor subtypes in the catecholamine-induced automatism in rat myocardium
D. C. Boer, J. W. M. Bassani, R.A. Bassani
Functional antagonism of ß-adrenoceptor subtypes in the catecholamine-induced automatism in rat myocardium
D. C. Boer, J. W. M. Bassani, R.A. Bassani
Fontes
British journal of pharmacology (Fonte avulsa) |