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 beta-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 beta(1)-, but not by alpha(1)-or beta(2)-adrenoceptor (AR) blockade. Similar alterations were seen in response to forskolin. However, responsiveness to 3-isobutyl-1-methylxanthine and CaCl(2) 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 beta(1)-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 response.
Penna
Larissa B
LB
Center for Biomedical Engineering and Department of Physiology and Biophysics/Biology Institute, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Bassani
Rosana A
RA
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D012044:Regression Analysis; D013312:Stress, Physiological / Q000502:physiology*
D018663:Adrenergic Agents; D010726:Phosphodiesterase Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine; D011224:Prazosin