EFFECTS OF INTRALUMINAL OR EXTRALUMINAL ENDOTHELIN ON PERFUSED RABBITBASILAR ARTERIES

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 (ox yHb). The basilar, mesenteric, and femoral arteries were isolated from 23 Japanese White rabbits. After isolation of the intra- and extralum inal sides of the preparation, 3 x 10(-10) to 3 x 10(-8) mol/L of ET w as administered intra or extraluminally. After extraluminal pretreatme nt 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 evalu ated 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 vasoconstrictin g effects on basilar arteries (p <0.01). The effect of ET on the basil ar arteries was significantly greater than on the femoral or mesenteri c 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 extra luminal indomethacin. Extraluminal oxyHb did not potentiate the contra ction induced by extraluminal ET. These results indicate that the sens itivity of the basilar artery to intraluminal ET is greater than that of the femoral or mesenteric artery. Endothelin may act as a potent va soconstrictor intra- as well as extraluminally under conditions such a s subarachnoid hemorrhage in which oxyHb is present in the extralumina l space and endothe hum-derived relaxing factors are inhibited.