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

Fundam Clin Pharmacol. 1999;13(2):180-6. doi: 10.1111/j.1472-8206.1999.tb00336.x.

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.

MeSH terms

  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / pharmacology*
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Denervation
  • Dogs
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Injections, Intravenous
  • Injections, Intraventricular
  • Male
  • Regional Blood Flow / drug effects
  • Sinoatrial Node / physiology
  • Tetrahydronaphthalenes / administration & dosage
  • Tetrahydronaphthalenes / pharmacology*

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Tetrahydronaphthalenes
  • amibegron