Effects of enkephalins, morphine, and naloxone on pial arteries during perivascular microapplication

The effects of the opiate receptor agonists, enkephalins and morphine, and the antagonist, naloxone, on cerebrovascular resistance vessels was investigated in situ by employing perivascular microapplication. Feline pial arteries with a resting diameter of 66-294 micron were tested. Vascular diameter was measured using television image splitting. Concentration-response curves revealed no change of diameter when Leu-enkephalin, D-Ala2-Leu-enkephalinamide, D-Ala2-Met-enkephalinamide, and morphine were applied in concentrations of 10(-11)-10(-5) M. Considering the concentrations of enkephalins that have been found in natural cerebrospinal fluid or that can be expected in the vicinity of enkephalinergic synapses, the data obtained with the lower concentrations indicate that enkephalins are probably not important for the regulation of pial arterial resistance. At 10(-4) M only the dilation (4.3%) elicited by D-Ala2-Leu-enkephalinamide was statistically significant (p less than 0.01). All four agonists at 10(-3) M induced significant dilatations varying between 5.4 and 13.6%. Naloxone exerted no vascular effect per se at 10(-5) and 10(-4) M but a dilatation of 15.3% at 10(-3) M. The latter can be explained by a partial agonist action. During simultaneous administration, naloxone (10(-4) M) reduced the dilatations induced by 10(-4) and 10(-3) M D-Ala2-Leu-enkephalinamide dose dependently. This indicates that mu- and delta-opioid receptors, probably located at the vascular smooth muscle cell, were involved in the mediation of the dilatation induced by the highest concentrations of the compounds.