Hyposensitivity to vasopressin in a hemorrhaged-transfused rat model of portal hypertension

Abstract

This study was designed to evaluate the hemodynamic response to vasopressin infusion during hemorrhage and blood transfusion in a rat model of portal hypertension. Portal pressure, arterial pressure, and regional and systemic blood flows were measured in a rat model of portal hypertension receiving placebo or vasopressin infusion. Effects of the drugs were compared in control rats and rats subjected to hemorrhage and blood transfusion. In a stable portal hypertensive rat group (no hemorrhage or transfusion) a standard vasopressin dose, 2.5 mU X kg-1 X min-1, resulted in a significantly lower portal pressure (11.5 +/- 0.7 vs. 14.4 +/- 0.6 mmHg) with a concomitantly lower portal venous inflow (8.5 +/- 0.3 vs. 11.1 +/- 0.6 ml X min-1 X 100 g body wt-1) when compared with rats receiving placebo. These findings are in contrast to the effects obtained with the same dose of vasopressin given during blood transfusion to hemorrhaged portal hypertensive rats. The standard dose of vasopressin had no effect on any of the splanchnic or systemic circulatory parameters. Only when a dose of vasopressin 10 times larger was used in the hemorrhaged-transfused animals were hemodynamic effects noted. A significant decrease in portal flow and pressure was noted. These findings suggest that vasopressin given during hemorrhage may be less effective than when given during a stable state. Larger doses of vasopressin may be needed during hemorrhage to produce the same effect as seen during a controlled stable state. Caution should be used in extrapolating the results of pharmacologic studies in stable portal-hypertensive models to hypovolemic states in humans.