Interaction of adrenergic and opioid systems in the short-term regulation of cardiovascular activities.

Endogenous opioid peptides such as methionine enkephalin (met-enkephalin) are known to have a profound cardiovascular action in addition to actions mimicking morphine in many animal models. In the anesthetized rabbit, met-enkephalin, as little as 1 microgram/kg, decreased blood pressure and heart rate upon its intravenous injection. Little is known about the locus of action or the mechanism and the physiological implication of the peptide action. The primary objective of this study was to test influences of adrenergic and cholinergic agents on the cardiovascular effects of the peptide. Pentobarbital (30 mg/kg) anesthetized rabbits were tracheotomized and a femoral artery and vein were cannulated for the measurement of arterial blood pressure and drug injection. Through a left lateral abdominal incision, the left renal nerve was isolated and renal nerve activity (RNA) recorded. Met-enkephalin (1 to 300 micrograms/kg, i.v.) decreased RNA initially and reduced blood pressure and heart rate. The cardiodepressant action of the peptide was antagonized by naloxone (1 mg/kg), but not by naloxone methobromide (1.3 mg/kg). Both phentolamine (4 mg/kg) and prazosin (1 mg/kg) antagonized the cardiovascular effect of met-enkephalin. Both hexamethonium (5 mg/kg) and mecamylamine (2 mg/kg) completely masked most of the depressant cardiovascular effects of metenkephalin by an increase in the duration of RNA suppression. The inability of naloxone methobromide and ganglionic blockers to antagonize the hypotensive action of met-enkephalin suggests that the peptide effect is secondary to its action on the central adrenergic system.