Ovine maternal and fetal cardiovascular effects of the serotonergic agonist R(-)-2,5-dimethoxy-4-methyl-amphetamine and characterization of serotonergic receptors in the ovine uterine and umbilical vessels

Pregnant ewes and their fetuses were instrumented between 110 to 120 days of gestation (term, 145 days) for monitoring heart rate, blood pressure, uterine artery blood flow, and fetal intra-abdominal umbilical artery blood flow and arterial blood gases. DOM (2,5-dimethoxy-4methyl-amphetamine) was administered intravenously to the ewe in doses of 1, 2.5, 5, 10, or 20 fig/kg. Maternal administration of DOM produced dose-dependent increases in maternal blood pressure and a fall in the heart rate. Uterine blood flow was dramatically decreased by DOM and uterine vascular resistance increased by 6.8, 16.7 and 19.6 fold after DOM at 5, 10, and 20 ftg/kg, respectively. These responses were accompanied by fetal hypoxemia, combined metabolic and respiratory acidosis, hypertension and bradycardia. The changes in blood flow and vascular resistance were always smaller in the fetal umbilical artery than those in the maternal uterine artery. The maximal rise in vascular resistance in the fetal umbilical artery was 2.6 fold after DOM (20 fig/kg). Ketanserin (1 mg/kg), administrated 30 minutes prior to the administration of DOM, inhibited maternal and fetal cardiovascular and blood gas responses to DOM. The conclusions are: (1) the fetus is distressed following maternal administration of DOM brought about by a ^Submitted to J. Pharmacol. Exp. Ther. as a research paper by Lubo Zhang, Donald C. Dyer, Frederick B. Hembrough and Miguel Isla.