Endothelial vasodilator production by uterine and systemic arteries. IV. Cyclooxygenase isoform expression during the ovarian cycle and pregnancy in sheep

Uterine artery endothelial production of the potent vasodilator, prostacycl in, is greater in pregnant versus nonpregnant sheep and in whole uterine ar tery from intact versus ovariectomized ewes, We hypothesized that uterine a rtery cyclooxygenase (COX)-1 and/or COX-2 expression would be elevated duri ng pregnancy (high estrogen and progesterone) and the follicular phase of t he ovarian cycle (high estrogen/low progesterone) as compared to that in lu teal phase (low estrogen/high progesterone) or in ovariectomized (low estro gen and progesterone) ewes, Uterine and systemic (omental) arteries were ob tained from nonpregnant luteal-phase (LUT; n = 10), follicular-phase (FOL; n = 11), and ovariectomized (OVEX; n = 10) sheep, as well as from pregnant sheep (110-130 days gestation; term = 145 +/- 3 days; n = 12). Endothelial and vascular smooth muscle (VSM) COX-1 protein levels and uterine artery en dothelial cell COX-1 mRNA levels were compared, Using immunohistochemistry and Western analysis, the primary location of COX-1 protein was the endothe lium; that is, we observed 2.2-fold higher COX-1 protein levels in intact v ersus endothelium-denuded uterine artery and a 6.1-fold higher expression i n the endothelium versus VSM (P < 0.05), COX-2 protein expression was not d etectable in either uterine artery endothelium or VSM, COX-1 protein levels were observed to be higher (1.5-fold those of LUT) in uterine artery endot helium from FOL versus either OVEX or LUT nonpregnant ewes (P < 0.05), with substantially higher COX-1 levels seen in pregnancy (4.8-fold those of LUT ), Increases in uterine artery endothelial COX-1 protein were highly correl ated to increases in the level of COX-1 mRNA (r(2) = 0.66; P < 0.01) for al l treatment groups (n = 6-8 per group), suggesting that increased COX-1 pro tein levels are regulated at the level of increased COX-1 mRNA, No change i n COX-1 expression was observed between groups in a systemic (omental) arte ry, In conclusion, COX-1 expression is specifically up-regulated in the ute rine artery endothelium during high uterine blood flow states such as the f ollicular phase and, in particular, pregnancy.