ENDOTHELIAL VASODILATOR PRODUCTION BY UTERINE AND SYSTEMIC ARTERIES .1. EFFECTS OF ANG-II ON PGI(2) AND NO IN PREGNANCY

Uterine vasculature is less responsive than systemic vasculature to an giotensin II (ANG II)-induced vasoconstriction. We hypothesized that p regnancy augments basal and ANG II-stimulated endothelial prostacyclin (PGI(2)) and/or nitric oxide (NO) production, which locally increase vascular smooth muscle (VSM) adenosine 3',5'-cyclic monophosphate (cAM P) and guanosine 3',5'-cyclic monophosphate (cGMP), respectively. Uter ine (UA) and systemic arteries (SA) from pregnant (P) and nonpregnant (NP) sheep were incubated with isobutylmethylxanthine. Basal PGI(2), c AMP, and cGMP production was 2.4-, 1.6-, and 5.9-fold greater (P < 0.0 1) in UA from P vs. NP sheep; endothelium removal lowered (P < 0.05) v alues 69, 44, and 88%. Basal SA PGI(2) and cAMP, but not cGMP, also we re elevated by pregnancy. Indomethacin (Indo; 100 mu M) decreased PGI( 2) and cAMP, but not cGMP production; N-omega-nitro-L-arginine methyl ester (L-NAME; 10 mu M) and methylene blue (MB, 10 mu M) only decrease d cGMP. Basal UA, but not SA, NO synthase activity (conversion of [H-3 ]arginine to [H-3]citrulline), was 1.8-fold higher in pregnancy and de creased (P < 0.01) after endothelium removal and with L-NAME. ANG II ( 50 nM) increased PGI(2) (86%) and cAMP (56%) production only in UA fro m P sheep (P < 0.05); this was abolished by endothelium removal or Ind o. ANG II also increased (P < 0.01) cGMP production by UA from both gr oups but only by SA from P ewes; this was absent in denuded, L-NAME-, or MB-treated vessels. Stimulation of VSM cGMP production with sodium nitroprusside (50 mu M) was inhibited by MB, but not L-NAME or endothe lium removal. In pregnancy, endothelial PGI(2) and NO production are e nhanced and may contribute to attenuated ANG II vasoconstriction via V SM cAMP and cGMP.