Effect of pregnancy on endothelium and smooth muscle: their role in reduced adrenergic sensitivity

Abstract

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the vascular endothelium on noradrenaline‐induced contractions in non‐pregnant and pregnant guinea‐pig uterine arteries

“…Further investigations are necessary to resolve this problem. However, it should be mentioned that these findings are in contrast with some reported previously (Weiner et al, 1991), but in agreement with the results obtained for human uterine radial arteries (Steel et al, 1993).…”

Upregulation of endothelial cell Ca2+signaling contributes to pregnancy-enhanced vasodilation of rat uteroplacental arteries

“…The basal activity of Ca 2ϩ -dependent eNOS of guinea-pig uterine arteries was upregulated fourfold in the course of pregnancy (53). Basal generation of NO was increased in uterine arteries of pregnant animals and attenuated the phenylephrine-induced vasoconstriction (17,29,49,(52)(53)(54). In a previous study of Gokina et al (18), inhibition of basal NO production with N -nitro-L-arginine, a potent inhibitor of NO synthase, significantly enhanced pressure-induced constriction of rat uteroplacental arteries.…”

“…Extensive studies have shown that late pregnancy is a state of increased basal and stimulated production of endotheliumderived vasodilators in the maternal uterine circulation (2,3,12,17,29,43,49,52). Uterine vasodilation, induced both by chemical (ACh) or mechanical stimulation (shear stress), was significantly enhanced during gestation, suggesting that some common mechanism(s) might underlie the pregnancy-induced adaptive changes in endothelial cell function (1,9,10,30,36,38,49,54).…”

Isolated mesenteric arteries from pregnant rats show enhanced flow‐mediated relaxation but normal myogenic tone.

“…In contrast it has been suggested that the blunted responses to pressor agonists in arteries from pregnant animals may be due to enhanced NO synthesis (Molnar & Hertelendy, 1992) and some argue that an increase in NO production may be confined to discrete circulations, e.g. uterine artery (Weiner, Liu, Thompson, Herrig & Chestnut, 1991) or the renal vascular bed (Danielson & Conrad, 1995). These studies all highlight the need to evaluate the response to flow in pregnancy, a more physiologically relevant stimulus to NO synthesis than ACh, bradykinin, histamine or other commonly used endothelium-dependent vasodilators.…”