Systemic and uterine vascular response to serotonin in third trimester pregnant ewes

Abstract

Released from aggregating platelets, serotonin (5HT) among other vasoactive components is considered to play an important role in preeclampsia, one of the most common medical complications of pregnancy. This study was designed to evaluate the simultaneous uterine and systemic vascular effects of systemically administered serotonin in pregnant sheep and compare them to the well known effects of angiotensin II and norepinephrine. Nine instrumented pregnant ewes received intravenous (inferior vena cava) infusions of increasing doses of serotonin, norepinephrine and angiotensin II in random order. Cardiac output, arterial blood pressure, heart rate, and uterine blood flow were recorded. Systemic administration of serotonin at doses of 2, 4, and 8 μg/kg body weight/min caused a slight increase in mean arterial blood pressure (1, 4 and 11%), a large decrease in uterine blood flow (10, 37, and 71%) but did not change cardiac output. Serotonin led to an increase in uterine vascular resistance with only small changes in systemic vascular resistance (UVR 17, 107, and 363% vs. SVR 3, 10 and 11%). In contrast, angiotensin II increased both systemic and uterine vascular resistance (SVR 16, 37, 56, and 95% and UVR 5, 16, 28 and 99%). Norepinephrine also raised both systemic and uterine vascular resistance, though to a different extent (SVR 5, 17, 37, and 118% vs. UVR 5, 46, 84 and 304%). Systemic infusions of serotonin in third trimester pregnant ewes resulted in uterine vasoconstriction. In contrast to the marked effect on the uterine vasculature, the systemic cardiovascular responses were small, thus demonstrating a nearly selective effect of serotonin on the uterine vasculature at the doses administered. Increased release and decreased metabolism of serotonin in preeclampsia therefore could lead to significant reductions in uteroplacental blood flow before hypertension occurs.