Endothelial nitric oxide release in isolated perfused ovine uterine arteries: effect of pregnancy

The present study was designed to determine the release of endothelial nitric oxide, measured as combined nitric oxide, nitrite and nitrate (NOx), in isolated perfused uterine arteries obtained from nonpregnant and pregnant sheep. Noradrenaline produced concentration-dependent increases in perfusion pressure in both nonpregnant and pregnant uterine arteries with pD2 values of 5.1+/-0.07 and 4.6+/-0.04, respectively. The maximum responses were 300.8+/-8.8 mmHg for nonpregnant arteries and 86.9+/-1.3 mmHg for pregnant ones. N(G)-nitro-L-arginine increased noradrenaline-mediated maximum response in the pregnant (86.9+/-1.3 to 144.6+/-5.1 mmHg), but not in the nonpregnant, uterine arteries. The basal level of NOx was significantly higher in pregnant than in nonpregnant uterine arteries (346.1+/-63.2 vs. 86.0+/-20.6 pmol/ml). The calcium ionophore A23187 and adenosine triphosphate produced concentration-dependent increases in NOx release in both nonpregnant and pregnant arteries. Compared to the nonpregnant tissue, the agonist-induced increase in NOx release was significantly enhanced in the pregnant uterine artery. In accordance, endothelial NO synthase protein expression in pregnant uterine artery was 197% of that in nonpregnant artery. These data indicate that in the uterine artery, pregnancy increases both basal and agonist-induced release of endothelial nitric oxide, which is likely to play a key role in attenuated vascular reactivity of the uterine artery to vasoconstrictors during the course of pregnancy.