Enkephalin lowers vascular resistance in dog hindlimb via a peripheral nonlimb site.
The intravenous administration of methionine enkephalin in anesthetized dogs produces an abrupt decline in mean arterial pressure, left ventricular pressure, and the maximal rate of left ventricular pressure development. All of these changes are prevented by receptor blockade with the opiate antagonist, naloxone. To evaluate peripheral vascular contributions to these responses, experiments were conducted in a constant pressure-isolated perfused hindlimb. In this model, the sharp decline in mean arterial pressure associated with enkephalin injection (5 micrograms/kg iv) coincided with an equally sharp decline in vascular resistance (rise in blood flow) in the hindlimb. Both were blocked by naloxone pretreatment (1 mg/kg). When equal doses of enkephalin were administered directly into the femoral inflow (external iliac artery), both arterial pressure and hindlimb flow responses were all but eliminated. This observation ruled out significant direct vascular interactions in the response and indicated a site of action outside the hindlimb. Additional catheters were placed in the bracheocephalic artery and descending aorta to permit the comparison of arterial injections conducted, respectively, into the cerebral or abdominal circulations. Injections introduced into the descending aorta consistently produced the greatest response, followed by injections (in descending order of effectiveness) into the jugular, the brachiocephalic, and external iliac. The response in the hindlimb vasculature was initiated at a site somewhere between the diaphragm and terminal aorta. The vascular response to enkephalin was subsequently eliminated by blocking ganglionic transmission with the nicotinic antagonist mecamylamine. These observations suggest that the opioids probably interrupt local vasomotor traffic via opiate receptors in regional sympathetic ganglia or in the spinal cord.
Caffrey
J L
JL
Department of Physiology, Texas College of Osteopathic Medicine, Fort Worth 76107.
Gu
H
H
Barron
B A
BA
Gaugl
J F
JF
D000818:Animals; D004285:Dogs; D004744:Enkephalin, Methionine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology*; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects*
D004745:Enkephalins; D009292:Narcotic Antagonists; D009270:Naloxone; D004744:Enkephalin, Methionine