Increased spontaneous activity and reduced inotropic response to catecholamines in ventricular myocytes from footshock-stressed rats

Exposure to stressors has been shown to change atrial responsiveness to catecholamines, but it is not clear yet how it affects the ventricular myocardium, which plays a major role in the catecholamine-stimulated increase in cardiac output. Adult male rats were submitted to restraint (RST) or footshock (FS) sessions for 3 days. Reactivity to agonists of the β-adrenergic pathway was analyzed in left ventricular myocytes isolated from stressed and control rats (CTR). Whereas no significant changes were detected after RST, enhancement of catecholamine-induced spontaneous activity, accompanied by decrease in inotropic maximal response, was observed in myocytes from FS rats. Changes were reversed by β1-, but not by α1- or β2-adrenoceptor (AR) blockade. Similar alterations were seen in response to forskolin. However, responsiveness to 3-isobutyl-1-methylxanthine and CaCl2 was comparable in control and FS groups. A significant negative correlation was observed between the maximally stimulated spontaneous activity rate and contraction amplitude. Results indicate that: (a) enhanced automatism during adrenergic stimulation of myocytes from FS rats is mediated by β1-ARs and seems to involve post-receptor mechanisms, probably decreased cAMP degradation; (b) the exaggerated spontaneous activity, which may contribute to generation of catecholaminergic arrhythmias, might limit the development of the inotropic response1317382CNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçã