Effects of a Stable Enkephalin Analogue, (D-Met2,Pro5)-Enkephalinamide, and Naloxone on Cortical Blood Flow and Cerebral Blood Volume in Experimental Brain Ischemia in Anesthetized Cats

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Abstract
The effects of intracarotid injection of the stable enkephalin analogue (d-Met2,Pro5)-enkephalinamide (ENK) and intravenous administration of naloxone on the cerebrocortical blood flow (dye dilution method) and cerebral blood volume (CBV) (photoelectric method) were investigated during unilateral brain ischemia in anesthetized cats. Both parameters were measured simultaneously in the intact and ischemic (middle cerebral artery occluded) hemispheres. An intracarotid injection of ENK 0.5 mg/kg induced a significant increase in cortical vascular resistance and a −87% decrease in cerebrocortical blood flow from 25 ± 3 to 4 ± 3 ml/100 g/min, without CBV alteration in the ischemic hemisphere. Naloxone (1 mg/kg i.v.), on the other hand, induced a marked two-fold increase in cerebrocortical blood flow and a significant elevation of CBV from 5.9 ± 0.5 to 7.4 ± 0.7 vol% in the ischemic hemisphere. No change in cerebrocortical blood flow or CBV was observed in the intact hemisphere either after ENK or after naloxone administration. Arterial blood gases and hematocrit remained unchanged. On the basis of the present findings, we conclude that (a) besides other factors, endogenous opioid mechanisms may also participate in ischemic cerebrovascular reactions and (b) the cerebral circulatory effects of naloxone probably reflect its opiate receptor blocking property and not simply its other non–opiate-related actions.