Uteroplacental production of eicosanoids in ovine pregnancy

Dramatic cardiovascular alterations occur during normal ovine pregnancy which may be associated with increased prostaglandin production, especially of uteroplacental origin. To study this, we examined (Exp 1) the relationships between cardiovascular alterations, e.g., the rise in uterine blood flow and fall in systematic vascular resistance, and arterial concentrations of prostaglandin metabolites (PGEM, PGFM and 6-keto-PGF_1α) in nonpregnant (n=4) and pregnant (n=8) ewes. To determine the potential utero-placental contribution of these eicosanoids in pregnancy, we also studied (Exp 2) the relationship between uterine blood flow and the uterine venous-arterial concentration differences of PGE₂, PGF_2α, PGFM, 6-keto-PGFP_1α, and YxB₂ in twelve additional late pregnant ewes. Pregnancy was associated with a 37-fold increase in uterine blood flow and a proportionate (27-fold) fall in uterine vascular resistance (p<0.01). Arterial concentrations of PGEM were similar in nonpregnant and pregnant ewes (316±19 and 245±37 pg/ml), while levels of PGFM and PGI₂ metabolites 6-keto-PGF_1α were elevated 23-fold (31±14 to 708±244 pg/ml) and 14-fold (12±4 to 163±78 pg/ml), respectively (p<0.01). Higher uterine venous versus uterine arterial concentrations were observed for PGE₂ (397±36 and 293±22 pg/ml) and 6-keto-PGF_1α (269±32 and 204±32 pg/ml), p<0.05, but not PGF_2α or TxB₂. Although PGFM concentrations appeared to be greater in uterine venous (1197±225 pg/ml) as compared to uterine arterial (738±150 pg/ml) plasma, this did not reach significance (0.05<p<0.1). In normal ovine pregnancy arterial levels of PGI₂ are increased, which may in part reflect increased uteroplacental production. Moreover the gravid ovine uterus also appears to produce PGE₂ and metabolize PGF_2α.