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.