Effect of vasoactive intestinal polypeptide on uterine blood flow in pregnant ewes

Vasoactive intestinal polypeptide has been localized in the uterine vasculature, uterine smooth muscle and the placenta of several species. Vasoactive intestinal polypeptide is a potent uterine vasodilator in nonpregnant sheep and also abolishes spontaneous uterine contractile activity, but the effects of this polypeptide on the uterine vasculature of the pregnant animal is currently unknown. The present experiments were performed in seven late-term pregnant sheep which were chronically catheterized to evaluate the uterine vascular effects of vasoactive intestinal polypeptide. An intra-arterial catheter was placed in a branch of the main uterine artery to allow administration of vasoactive intestinal polypeptide directly into the uterine vasculature. Uterine blood flow was continuously monitored via an electromagnetic flow transducer on both main uterine arteries. Vasoactive intestinal polypeptide infused at the rate of 1 to 30 micrograms/min produced dose-related reductions in uterine blood flow (33% +/- 9% at 30 micrograms/min). This decrease was due to a reduction in systemic arterial blood pressure, since calculated resistance in the uterine vasculature that received the vasoactive intestinal polypeptide did not change significantly. In addition, the contralateral uterine vasculature that did not receive direct intra-arterial infusions of vasoactive intestinal polypeptide showed identical changes. These data suggest that vasoactive intestinal polypeptide produces peripheral vasodilation at doses which have very little uterine effect locally. These data can be interpreted to mean either that high local endogenous production of vasoactive intestinal polypeptide prevents exogenously administered vasoactive intestinal polypeptide from exerting its vascular effects, or that vasoactive intestinal polypeptide is a very weak uterine vasodilator in pregnant ewes. The clarification of these possibilities will require further experimentation.