SYSTEMIC AND UTERINE VASCULAR-RESPONSE TO SEROTONIN IN 3RD TRIMESTER PREGNANT EWES

Released from aggregating platelets, serotonin (5HT) among other vasoa ctive components is considered to play an important role in preeclamps ia, one of the most common medical complications of pregnancy. This st udy was designed to evaluate the simultaneous uterine and systemic vas cular effects of systemically administered serotonin in pregnant sheep and compare them to the well known effects of angiotensin II and nore pinephrine. Nine instrumented pregnant ewes received intravenous (infe rior vena cava) infusions of increasing doses of serotonin, norepineph rine and angiotensin II in random order. Cardiac output, arterial bloo d pressure, heart rate, and uterine blood flow were recorded. Systemic administration of serotonin at doses of 2, 4, and 8 mu g/kg body weig ht/min caused a slight increase in mean arterial blood pressure (1, 4 and 11%), a large decrease in uterine blood now (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 resi stance (UVR 17, 107, and 363% vs. SVR 3, 10 and 11%). In contrast, ang iotensin II increased both systemic and uterine vascular resistance (S VR 16, 37, 56, and 95% and UVR 5, 16, 28 and 99%). Norepinephrine also raised both systemic and uterine vascular resistance, though to a dif ferent extent (SVR 5, 17, 37, and 118% vs. UVR 5, 46, 84 and 304%). Sy stemic infusions of serotonin in third trimester pregnant ewes resulte d 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 ute rine vasculature at the doses administered. Increased release and decr eased metabolism of serotonin in preeclampsia therefore could lead to significant reductions in uteroplacental blood flow before hypertensio n occurs.