This study investigated the effect of vasopressin on portal-systemic collaterals in portal hypertensive rats and the influence of nitric oxide (NO) and prostaglandin on the responsiveness of collateral vessels to vasopressin. The vascular responsiveness to graded concentrations of vasopressin was tested with or without the incubation of n -nitro-L-arginine (NNA) (100 mol/L) and/or indomethacin (10 mol/L) in perfused collateral vascular beds of rats with portal hypertension induced by partial portal vein ligation. In addition, concentration-response curves to vasopressin with incubation of a vasopressin V 1 receptor antagonist d(CH 2 ) 5 Tyr(Me) arginine vasopressin and concentrationresponse curves to a V 2 receptor agonist 1-desamino-8-Darginine vasopressin were performed. Vasopressin significantly increased the perfusion pressure of collaterals, and this effect was suppressed by the addition of the V 1 receptor antagonist. Perfusion with the V 2 receptor agonist had no effect on the collaterals. Incubation with NNA, indomethacin, or both significantly potentiated the response of collaterals to vasopressin. In addition, the pressor response to vasopressin in the combination group was significantly higher than that in the NNA-alone group. The results show that vasopressin produces a direct vasoconstrictive effect on the portal-systemic collaterals of portal hypertensive rats. This effect is mediated by the vasopressin V 1, but not V 2 , receptors. The attenuation of the response to vasopressin by NO and prostaglandin suggest a function role of both mediators in the regulation of the portal-systemic collateral circulation in portal hypertensive rats. (HEPATOLOGY 1999;30:630-635.)Vasopressin, an agent that decreases portal and collateral blood flow and portal pressure, 1 has been used in cirrhotic patients for the management of esophageal variceal bleeding. 2 It is a powerful vasoconstrictor and exerts varying degree of contractile effect over arteries and veins. 3 Perfusion studies of splanchnic vascular beds have shown that vasopressin markedly increases the vascular resistance of mesenteric arteries but does not alter the venous resistance. 4 Therefore, the constriction of splanchnic arteries accompanied by the reduction of splanchnic and portal-systemic collateral blood flow have been postulated to be the major mechanisms by which vasopressin alleviates portal hypertension and controls variceal hemorrhage in patients with cirrhosis. However, it is uncertain if the effect of vasopressin on reducing collateral blood flow is also mediated by a direct vasoconstrictive effect on the collateral vascular beds.Nitric oxide (NO) and prostacyclin (PGI 2 ) are endogenous vasodilators synthesized by the vascular endothelium. 5,6 Both of them modulate mesenteric vascular tone and are important contributors to splanchnic hyperemia in portal hypertensive rats. [7][8][9][10][11] In addition, NO plays a role in modulating collateral vascular resistance, 12 and increased PGI 2 activities have been observed in systemic circulatio...

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