Effects of intraluminal or extraluminal endothelin on perfused rabbit basilar arteries.

Abstract

The authors investigated selective intra- and extraluminal effects of endothelin (ET) on perfused basilar and extracranial arteries and also studied the interaction between ET and extraluminal oxyhemoglobin (oxyHb). The basilar, mesenteric, and femoral arteries were isolated from 23 Japanese White rabbits. After isolation of the intra- and extraluminal sides of the preparation, 3 x 10(-10) to 3 x 10(-8) mol/L of ET was administered intra- or extraluminally. After extraluminal pretreatment with 10(-5) mol/L oxyHb, 10(-5) mol/L N(G)-monomethyl-L-arginine (L-NMMA), or 10(-6) mol/L indomethacin, 10(-10) to 10(-8) mol/L of ET was administered intra- or extraluminally. Arterial contraction was evaluated by measuring the increase in the perfusion pressure gradient with a differential pressure gauge. Both intra- and extraluminal ET (10(-9) to 3 x 10(-8) mol/L) showed potent and dose-dependent vasoconstricting effects on basilar arteries (p < 0.01). The effect of ET on the basilar arteries was significantly greater than on the femoral or mesenteric arteries (both p < 0.01). The effect of intraluminal ET was enhanced by extraluminal oxyHb (p < 0.05) and L-NMMA (p < 0.01), but not by extraluminal indomethacin. Extraluminal oxyHb did not potentiate the contraction induced by extraluminal ET. These results indicate that the sensitivity of the basilar artery to intraluminal ET is greater than that of the femoral or mesenteric artery. Endothelin may act as a potent vasoconstrictor intra- as well as extraluminally under conditions such as subarachnoid hemorrhage in which oxyHb is present in the extraluminal space and endothelium-derived relaxing factors are inhibited.