Chronic Blockade of Nitric Oxide Synthase and Endothelin Receptors During Pregnancy in the Rat: Effect on Reactivity of the Uterine Artery In Vitro.

Objective: To investigate the effects of chronic blockade of nitric oxide (NO) production and endothelin (ET-1) receptor antagonism on edothelial and vascular smooth muscle function of the uterine artery in vitro obtained from nonpregnant and pregnant rats.Methods:Pregnant or nonpregnant Wistar rats wee either treated orally for up to 18 days with the NO synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME), the ETA-/ETB-receptor antagonist bosentan, or both, or they received no treatment (controls). Absolute contractile force as well as endothelium-dependent and -independent vascular reactivity of uterine arteries were determined in vitro. Isometric tension was recorded. ANOVA and the Mann-Whitney U test were used for statistical analysis.Results:Pregnancy increased obsolute tension (mN/mm) elicited in uterine arteries by ET-1 (P < .01), serotonin (P < .05), norepinephrine (P < .02), and KCl (P < .0001). Chronic treatment with L-NAME or L-NAME plus bosentan, but not with bosentan alone, reduced contractions to KCl in pregnant and nonpregnant rats (P < .005-.0001), while pregnancy-induced enhancement in tension development remained unchanged in all groups (P < .005). After exposure of uterine arteries to L-NAME in vitro, vascular sensitivity to ET-1 was augmented in uterine arteries of pregnant but not of nonpregnant animals (P < .05).L-NAME-pretreatmetn did not influence the pregnancy-induced increase of vascular sensitivity to acetylcholine but reduced maximal relaxation in nonpregnant animals (P < .05). In addition, pregnancy diminished sensitivity of uterine arteries to sodium nitroprusside (P < .002), which was abolished by chronically administered L-NAME. Bosentan had no influence on vasodilation in vitro.Conclusion:Neither endothelin-1 nor nitric oxide seem to contribute to the augmented tension to depolarization and receptor-operated stimulation of vascular smooth muscle cells in rat uterine arteries during pregnancy. In addition, pregnancy is associated with increased NO production in uterine arteries, as evidenced by augmented endothelium-dependent relaxations, increased NO release by endothelin-1, and decreased sensitivity to sodium nitroprusside. [ABSTRACT FROM PUBLISHER]