Effects of vasopressin on portal-systemic collaterals in portal hypertensive rats: Role of nitric oxide and prostaglandin

Abstract

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...

Endothelin–1 Induces Vasoconstriction on Portal–Systemic Collaterals of Portal Hypertensive Rats

“…37 Recently, prostaglandin was found to be involved in the modulation of collateral vascular tone in portal hypertensive rats and could modify the vasoconstrictive effect of vasopressin. 19 In this study, we found that incubation with indomethacin, NNA, or both significantly increased the collateral response to ET-1. These results suggest that both NO and prostaglandin are important factors involved in the attenuation of vascular response to ET-1 in portal-systemic collaterals.…”

“…The in situ perfusion system was performed as described in previous reports. 18,19 Both jugular veins were cannulated with 16-gauge Teflon cannulas to ensure an adequate outflow without any resistance even at the highest flow rates. Heparin (200 /100 g body weight) was injected through one of the cannulas.…”

“…Because the temperature and pressure of the system stabilized within 20 minutes, all the experiments were performed 25 minutes after starting perfusion at a constant rate of 20 mL/min. 18,19 Only one concentration-response curve was performed in each preparation. In individual preparation, the contracting capability of the collateral vessels was challenged with a 125-mmol/L potassium chloride solution after testing experimental agents.…”

Portal systemic collateral development: Is it a trophic adaptation mechanism to hepatic deprivation?

“…These authors have previously demonstrated the vasoconstrictor effect of vasopressin, endothelin-1 (ET-1) and somatostatin on the collateral vessels in partial portal vein ligatedrats. [8][9][10][11][12] They also reported the vasoconstrictor action of ET-1 on the collaterals of bile duct-ligated cirrhotic rats. 13 The common triggering factor for both cirrhotic and noncirrhotic portal hypertension is an increased resistance to portal venous flow.…”

“…Therefore, normalization of elevated portal pressure can be achieved by correcting the elevated portal resistance in the portal collateral circulation (the 'backward' hypothesis). 4,30 This is the basis of several experimental studies on the effects of different vasoactive substances and drugs on blood flow, the resistance to portal-systemic collaterals, [6][7][8][9][10][11][12][13][34][35][36][37] and their applications in the medical treatment of patients with cirrhosis. 32,38,39 If establishing the significance of alterations associated with portal hypertension could help to elucidate the mechanisms involved in its production and maintenance, we could, then, speculate on the hypothetical purpose of the splanchnic response in portal hypertension.…”