Effects of nitric oxide and cyclooxygenase inhibition on splanchnic hemodynamics in portal hypertension.

Portal hypertension is associated with splanchnic hyperemia and increased plasma levels of prostacyclin. Recently, nitric oxide was proposed as a mediator of this arterial vasodilatation. We hypothesized that portal hypertension alters the relative contribution of prostacyclin and nitric oxide to splanchnic vasomotor control. We studied the relationship of nitric oxide and prostaglandins in normal and portal-hypertensive (3 wk after partial portal vein ligation) male rabbits at baseline and following increasing doses of indomethacin, LG-nitro-L-arginine methylester or both. L-arginine was used as the control. Aortic, central and portal venous pressures were measured directly. Blood flow in the superior mesenteric artery was measured by means of an ultrasonic flow probe, and resistance was calculated. LG-nitro-L-arginine methylester produced vasoconstriction (increased resistance and decreased blood flow in the superior mesenteric artery) in normal and portal-hypertensive rabbits, although in portal hypertensive animals resistance and superior mesenteric artery blood flow remained significantly different than that in normal rabbits because of preexisting hyperemia. L-arginine reversed the effect of LG-nitro-L-arginine methylester. Cyclooxygenase blockade induced dose-dependent vasoconstriction in normal and portal-hypertensive animals. Indomethacin induced further vasoconstriction after LG-nitro-L-arginine methylester and reduced portal venous pressure in portal-hypertensive animals. We conclude that this indicates an amplified role for some prostaglandin, probably prostacyclin, in portal hypertension hemodynamics. It also implies that the two vasodilators act by way of independent mechanisms.