Interaction between endothelium-derived nitric oxide and SIN-1 in human and porcine blood vessels.
Nitric oxide (NO) is a potent vasodilator and inhibitor of platelet function that is produced from L-arginine in endothelial cells. The mechanism of action of nitrovasodilators such as SIN-1 has striking similarities with endothelium-derived nitric oxide. We studied the effects and interactions of endothelium-derived relaxing factor with SIN-1 in isolated human internal mammary arteries, saphenous veins, and porcine coronary arteries. In human arteries, SIN-1 induced potent relaxations (IC50 value of 6.6 +/- 0.1; maximal response of 100%) that were comparable to that induced by acetylcholine and were augmented by removal of the endothelium (concentration shift of 3.2-fold; n = 8 and 6, respectively, p less than 0.05). The relaxation to SIN-1 was also enhanced in saphenous veins as compared to mammary arteries (concentration shift of 6.3-fold; n = 7 and 6, respectively, p less than 0.005). In human and porcine arteries, incubation with the false precursor substance of endothelium-derived NO, L-NG-monomethylarginine (10(-5) and 10(-4) M), enhanced the relaxation induced by SIN-1 (concentration shift of 3.2- and 2.5-fold, respectively; n = 4 to 6; p less than 0.05). Thus, SIN-1 is a potent vasodilator of human and porcine blood vessels. Its effects are attenuated by spontaneously released endothelium-derived NO.
Lüscher
T F
TF
Department of Medicine, University Hospital, Basel, Switzerland.
Richard
V
V
Yang
Z H
ZH
D000704:Analysis of Variance; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects*; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D012377:Rodentia; D012501:Saphenous Vein / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine