Intestinal vascular sensitivity to vasopressin in portal hypertensive rats

The intestinal vascular responsiveness to arginine vasopressin was evaluated in rats with chronic portal hypertension. Male Sprague-Dawley rats were made portal hypertensive by stenosis of the portal vein. Ten to twelve days after the induction of chronic portal hypertension, the responsiveness of the small intestinal circulation to cumulative doses of vasopressin was evaluated using an isolated pump-perfused small intestinal preparation. The ED50 for maximal vasoconstriction was increased twofold in portal hypertensive rats compared with control rats. To determine if the impaired responsiveness to arginine vasopressin was related to the hyperglucagonemia of chronic portal hypertension, plasma glucagon levels were elevated in normal rats to levels previously measured in portal hypertensive rats (i.e. approximately 450 pg/mL), and the dose response studies were repeated. Glucagon significantly attenuated the responsiveness of the intestinal vasculature to vasopressin. Equipotent doses of nitroprusside also attenuated intestinal vascular responsiveness to vasopressin. The results indicate that there is a reduced vascular sensitivity to vasopressin in the intestine of portal hypertensive animals and suggest that elevations in circulating vasodilators in portal hypertensive conditions may partially explain this altered vascular responsiveness.