Effects of propofol on substance P-induced relaxation in isolated human omental arteries and veins

To elucidate if an effect of propofol on endothelium-dependent relaxation could contribute to propofol-induced vasodilation, smooth muscle relaxation of isolated human omental artery and vein segments precontracted by endothelin-1 were measured. Substance P induced a concentration-dependent relaxation (mean +/- SEM) in both artery (63 +/- 8.4% of precontraction, n = 9) and vein (60 +/- 11%, n = 7). The relaxation was enhanced by 10(-6) m propofol (artery, 72 +/- 9.5%, n = 9; vein, 81 +/- 12%, n = 7) but not affected by 10(-7), 10(-5) and 10(-4) m propofol. In the presence of N-omega-nitro-l-arginine methyl ester (nitric oxide synthase inhibitor), 10(-6) m propofol still enhanced the substance P-induced relaxation in arteries but not veins, whereas 10(-4) m propofol inhibited the relaxation in both arteries (rightward shift of the concentration-response curve) and veins (28 +/- 7.5%, n = 8). In the presence of potassium chloride (to prevent hyperpolarization), the enhancement of substance P-induced relaxation by 10(-6) m propofol was abolished in both arteries and veins whereas 10(-5) and 10(-4) m propofol reduced the relaxation in arteries (38 +/- 13% at 10(-5) m, n = 6; 30 +/- 11% at 10(-4) m, n = 6) but not in veins. These results demonstrate that propofol, at lower, clinically relevant concentrations, promotes endothelium-dependent relaxation mediated via hyperpolarization in human omental arteries and via both nitric oxide and hyperpolarization in human omental veins.