Endothelium-derived relaxant factor inhibits effects of nitrocompounds in isolated arteries.
We investigated the influence of endothelial cells on the smooth muscle vasodilator effects to sodium nitroprusside (SNP) or Teopranitol (an organic mononitrate) in isolated segments of rabbit aorta and femoral artery. In the femoral artery, the vasodilator responses to both nitrocompounds were significantly higher in the absence of endothelial cells or after pretreatment with the endothelium-derived relaxant factor (EDRF) inhibitor nordihydroguaiaretic acid (NDGA; 10 microM). Moreover, under conditions of stimulated EDRF release (induced by acetylcholine; 30-100 nM) the vasodilator responses to SNP were further attenuated in vessels with intact endothelium. By contrast, in the rabbit aorta, the vasodilator responses to the nitrocompounds were not significantly altered by either endothelium removal or treatment with NDGA. However, in the presence of the EDRF stimulator acetylcholine, the dose-response curve to SNP was shifted to right in the aorta as well. The role of EDRF in the endothelium-mediated attenuation of the dilator potency of SNP was further investigated by using EDRF released from cultured (bovine aortic) endothelial cells. The dilator effects of SNP were compared in endothelium denuded femoral or aortic segments in the presence or absence of EDRF. The vasodilator effects of SNP in both types of arteries were significantly reduced in the presence of EDRF. We conclude that EDRF attenuates the arterial vasodilation induced by SNP and Teopranitol. The results further suggest that endothelial cells exhibit a greater basal release of EDRF in the femoral artery than in the aorta, since under unstimulated conditions an EDRF-induced attenuation was seen only in femoral and not in aortic segments.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D009569:Nitric Oxide; D009574:Nitro Compounds / Q000037:antagonists & inhibitors*; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D013402:Sugar Alcohols / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D009574:Nitro Compounds; D013402:Sugar Alcohols; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C042286:teopranitol; D009637:Masoprocol; D000109:Acetylcholine