Prostacyclin produced by the pregnant uterus in the dog may act as a circulating vasodepressor substance.

Abstract

A B S T R A C T Uterine production of PGI2 (prostacyclin) was quantitated in late pregnant dogs to evaluate if PGI2 could act as a circulating vasodepressor substance in pregnancy. In five anesthetized, laparotomized dogs, the uterine venous plasma concentration of 6-keto PGF,a (the in vitro hydrolysis product of PGI2) was 6.7±1.9 nglml and the arterial plasma concentration was 2.6±0.8 ng/ml. In four nonpregnant female dogs the arterial plasma concentration of 6-keto PGFi,a was consistently below 0.2 ng/ml. In eight pregnant dogs we also evaluated the ability of the pregnant uterus to inactivate PGI2 by comparing the hypotensive response to increasing doses of PGI2 infused into the uterine artery to the hypotensive response to increasing doses of PGI2 infused into the inferior vena cava. In addition, the effect of PGI2 infused into the uterine artery on uterine blood flow and intraamniotic fluid pressure was evaluated. The dose-response curves of intrauterine and intravenous PGI2 in causing systemic hypotension were identical suggesting that the pregnant uterus does not inactivate infused PGI2. Intrauterine PGI2 had no consistent effect on uterine hemodynamics although it did increase intraamniotic fluid pressure significantly. These data demonstrate that the pregnant uterus has the capacity to produce large quantities of PGI2 which is not inactivated in the uterus and therefore can appear in the arterial blood to exert a systemic vasodepressor effect.

The Onset of Breathing at Birth Stimulates Pulmonary Vascular Prostacyclin Synthesis

“…Previously, we have reported that, using identical methods to those used in the present study, fetal pulmonary arterial prostacyclin concentrations are more than four times higher than those of the ewe (18); and pregnant animals have elevated plasma prostacyclin when compared to nonpregnant (7,21). Late pregnant human venous plasma 6-keto-PGF,, concentration (244 pg/ml) determined by gas chromatography-mass spectrometry (21) is similar to the concentration we obtained from arterial plasma of near term pregnant ewes ( 105 pg/ml of blood = 175 pg/ml plasma when hematocrit = 40%) ( 18).…”

Furosemide increases urine 6-keto-prostaglandin F1 alpha. Relation to natriuresis, vasodilation, and renin release.

“…While plasma concentrations of up to 160 pg/ml have been reported in humans, 41 none was detectable in nonpregnant dogs. 42 More recent studies suggest that levels in humans are also very low. 43 In any event, intravenous infusion of labelled PGI 2 or 6-ketoPGF la in man or monkey, leads to the appearance of less than 15% of injected material as urine 6-ketoPGF^.…”

Effect of Captopril on Uterine Blood Flow and Prostaglandin E Synthesis in the Pregnant Rabbit

“…The high plasma PGE2 is associated with elevated urinary PGE2 excretion, a reflection of increased renal synthesis (6), so the kidneys may be a source of the elevated plasma PGE2. However, the uterus of pregnant animals (7) and women (8) contains high concentration of renin and high concentrations of PGE2 and PGI2 have been reported in the uterine vein of pregnant animals (2,9). Whether increased uterine synthesis of these compounds contributes to the elevated plasma concentration seen in human pregnancy is unclear.…”