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Peripheral cardiovascular actions of SR 58611 A, a beta 3‐adrenoceptor agonist, in the dog: lack of central effect

Abstract— In order to investigate the putative role of beta3‐adrenoceptors in central and peripheral cardiovascular regulations, the effects of intracisternal (i.c.) and intravenous (i.v.) injections of SR 58611 A (10, 50, 100 and 200 nmol kg−1), a selective beta3‐adrenoceptor agonist, were investigated in chloralose anaesthetized dogs. In normal dogs, i.v. SR 58611 A (100 and 200 nmol kg−1) induced a dose‐dependent increase in heart rate with no change in blood pressure. After i.c. injection, SR 58611 A failed to modify blood pressure and heart rate (except at the highest dose 200 nmol kg−1 which induced a positive chronotropic effect). The positive chronotropic effect of SR 58611 A (200 nmol kg−1) appeared earlier and was significantly more pronounced after i.v. than i.c. administration. The positive chronotropic effect of i.v. SR 58611 A (200 nmol kg−1) was reduced by pretreatment with beta‐adrenoceptor antagonists [propranolol, nadolol, bupranolol or the beta3‐adrenoceptor selective antagonist, SR 59230 A (2 mg kg−1 i.v.)] and suppressed after sinoaortic denervation (i.e. after removal of vagal tone to the heart). These experiments do not show evidence for a primary central cardiovascular effect of SR 58611 A. The positive chronotropic effect of i.v. SR 58611 A is mainly of peripheral origin and can be attributed to a baroreceptor‐mediated reflex due to the beta3‐adrenoceptor mediated vasodilation with an increase in sympathetic tone and a reduction in vagal tone to the heart.