Effects of enkephalins and the analogue FK-33824 on mean arterial pressure and heart rate in conscious sheep

Abstract

Experiments were designed to evaluate the central and systemic effects by enkephalins and the enkephalin analogue FK-33824 on mean arterial pressure (MAP) and heart rate (HR) in conscious sheep. Intracerebroventricular infusion of FK-33824 increased both MAP and HR in a dose-dependent manner in normal sheep. The increases in MAP and HR were attenuated by naloxone administered centrally, but not systemically. Intracerebroventricular infusion of met-enkephalin, leu-enkephalin and naloxone failed to change both MAP and HR significantly. However, intravenous infusion of met-enkephalin, leu-enkephalin and FK-33824 resulted in bradycardia. Haemorrhage alone decreased both MAP and HR. Intracerebroventricular infusion of FK-33824 blunted the reduction in MAP in response to haemorrhage. The increases in MAP and HR following FK-33824 were also accompanied by elevated levels of plasma renin concentration. It is suggested that the tachycardia and pressor effect produced by the intracerebroventricular administration of FK-33824 in normal conscious sheep may result from a combined action of both neural and chemical pathways which are involved in cardiovascular control, and are mediated via the mu-opioid receptors. Opioids may have opposite effects on cardiovascular control depending on the route of administration.