Functional antagonism of β‐adrenoceptor subtypes in the catecholamine‐induced automatism in rat myocardium

BACKGROUND AND PURPOSEMyocardial 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 APPROACHThe 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 RESULTSCatecholaminergic automatism was Ca2+‐dependent, as it required a functional sarcoplasmic reticulum to be exhibited. Although both α‐ and β‐adrenoceptor activation caused inotropic stimulation, only β1‐adrenoceptors seemed to mediate the induction of spontaneous activity. Catecholaminergic automatism was enhanced and suppressed by β2‐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 β2‐adrenoceptor stimulation.CONCLUSIONS AND IMPLICATIONSα‐ and β2‐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 β1‐ and β2‐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 β2‐adrenoceptor stimulation.