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.