Effects of long-term octreotide treatment on the response of portal-systemic collaterals to vasopressin in portal hypertensive rats.

Abstract

Chronic portal hypertension is associated with the development of portal-systemic collaterals. Long-term octreotide treatment has been shown to enhance the constrictive response to vasopressin in the mesenteric arteries of portal hypertensive rats. This study investigated the effects of long-term octreotide treatment on the response of portal-systemic collaterals to vasopressin in portal hypertensive rats. Partially portal vein-ligated rats were divided into two groups to receive subcutaneous injection of either placebo (5% dextrose in water) or octreotide (30 microg kg(-1)) twice daily for 7 days. Two series of experiments were performed to measure: (a) the systemic and portal hemodynamics and cumulative concentration-response curves of collateral vessels to vasopressin (10(-10) to 10(-7 )M) and (b) the slopes of the flow-pressure curves of collaterals (an index of portal-systemic shunting). The cumulative concentration-response curves and flow pressure curves were determined by the in situ collateral perfusion. Long-term octreotide treatment significantly lowered the portal pressure without changes in the mean arterial pressure. Vasopressin significantly and similarly increased the perfusion pressure of collateral vessels in both the placebo- and octreotide-treated groups. In addition, long-term octreotide treatment exerted no effect on the EC(50) of vasopressin (-8.25 +/- 0.19 vs. -8.20 +/- 0.10, P > 0.05) and the slopes of flow-pressure curves (0.97 +/- 0.02 vs. 0.94 +/- 0.04, P > 0.05) in the collaterals. Despite lowering the portal pressure, long-term octreotide treatment did not enhance the vasoconstrictive effect of vasopressin in the collateral vessels of portal hypertensive rats and ameliorate the degree of portal-systemic shunting.