Pregnancy reduces serotonin-induced contraction of guinea pig uterine and carotid arteries.

Abstract

Because platelet activation and serotonin have been implicated in preeclamptic hypertension, we investigated the effect of pregnancy on the contractile response to this agent. Prior studies have shown that the vascular contractions to norepinephrine, angiotensin II, and thromboxane are reduced during normal pregnancy by the altered release of endothelium-derived vasoactive substances. We hypothesized that the contraction to serotonin would also be reduced during pregnancy by an endothelium-dependent mechanism. Isolated ring segments from uterine and carotid arteries of near-term pregnant and nonpregnant guinea pigs were studied after stimulating a small amount of active tone with prostaglandin F2 alpha. Serotonin (10(-8) to 10(-5) M) contractile responses of both arteries were reduced by pregnancy. Regardless of pregnancy status, the contractile responses of the uterine artery to serotonin were severalfold greater than that of the carotid artery whose maximum averaged only 10% of the 120 mM KCl contraction. Denudation of uterine artery abolished acetylcholine-stimulated relaxation in vessels from pregnant and nonpregnant animals. However, serotonin-induced contractions were enhanced by denudation only in ring segments obtained from pregnant animals. Nitric oxide synthase inhibition by either NG-monomethyl-L-arginine (L-NMMA) or N omega-nitro-L-arginine and cyclooxygenase inhibition by indomethacin had no effect on serotonin-induced contraction of intact uterine artery regardless of pregnancy. L-NMMA modestly enhanced the intact carotid arterial response to 10(-5) M serotonin independent of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)