Reduction by phentolamine of the hypotensive effect of methionine enkephalin in anaesthetized rabbits

Abstract

In intact rabbits anaesthetized with pentobarbitone, methionine enkephalin (Met enkephalin, 1-1,000 micrograms kg-1 i.v.) produced a dose-dependent bradycardia and hypotension. The bradycardia and hypotension were antagonized by naloxone hydrochloride (1 mg kg-1), but not by naloxone methobromide (1.3 mg kg-1). Phentolamine (1 and 4 mg kg-1 i.v.) blocked both the hypotension and bradycardia produced by Met enkephalin. The inhibitory effect of phentolamine was not due to a simple hypotensive action of this drug per se because a similar degree of hypotension induced by nitroprusside (15 micrograms kg-1, i.v.) caused a further reduction of pressure when Met enkephalin was added. Atropine (2 mg kg-1) reduced the bradycardia but not the hypotensive response to Met enkephalin. Met enkephalin did not antagonize the vasopressor effect of exogenous noradrenaline (2-8 micrograms kg-1, i.v.). Met enkephalin had no significant effects in superfused thoracic aortic strips and in isolated perfused hearts of rabbits. It is concluded that the cardiovascular effects of Met enkephalin are more probably due to an action on the central nervous system, although a peripheral site of action cannot be completely excluded.