EFFECT OF PREGNANCY ON ENDOTHELIUM AND SMOOTH-MUSCLE - THEIR ROLE IN REDUCED ADRENERGIC SENSITIVITY

During pregnancy, vascular reactivity of the uterine artery is characterized by decreased contraction to norepinephrine and increased relaxation to acetylcholine. We investigated whether 1) relaxation to A23187 is increased during pregnancy and 2) endothelium-derived relaxing factor (EDRF) and/or prostaglandins are responsible for the decreased uterine artery sensitivity to norepinephrine during pregnancy. Isolated rings of uterine and carotid arteries were obtained from pregnant and nonpregnant guinea pigs. Relaxation to sodium nitroprusside in uterine but not carotid artery was reduced during pregnancy. Relaxation of both uterine and carotid arteries to the calcium ionophore A23187 was unaffected by pregnancy. During pregnancy, contractions to norepinephrine were reduced in the uterine artery compared with arteries from nonpregnant animals. Indomethacin slightly enhanced the contractions of uterine artery to norepinephrine during pregnancy. However, indomethacin-treated uterine arteries from pregnant animals were still less responsive to norepinephrine than control uterine arteries from nonpregnant animals. Methylene blue enhanced the efficacy of norepinephrine in uterine arteries of nonpregnant animals as well as carotid arteries of pregnant and nonpregnant animals but not in uterine arteries of pregnant animals. In contrast, N-monomethyl-L-arginine, a specific inhibitor of EDRF synthesis, not only enhanced uterine and carotid artery responses to norepinephrine in both pregnant and nonpregnant animals but fully reversed the blunted potency of norepinephrine on uterine arteries of pregnant to that of nonpregnant animals. We conclude that 1) pregnancy-associated changes in endothelial function alter the contractile response to norepinephrine, 2) the effect of pregnancy is specific for the uterine compared with the carotid artery, 3) the decreased sensitivity of uterine artery to norepinephrine during pregnancy is secondary to increased EDRF, 4) the decreased response to sodium nitroprusside during pregnancy is consistent with increased basal release of EDRF, and 5) the pregnancy-associated increase in acetylcholine relaxation but lack of an effect on A23187-induced relaxation suggests a receptor-mediated phenomenon is involved.