Effect of pregnancy on contraction and endothelium-mediated relaxation of renal and mesenteric arteries

Abstract

We have hypothesized that differences in the effect of pregnancy on mechanisms modulating vascular reactivity underlie the redistribution of cardiac output. Because pregnancy increases mesenteric blood flow by 75% and renal blood flow by only 10% in the guinea pig, we investigated the effect of pregnancy on vascular reactivity in these two beds. Relaxation in response to acetylcholine (ACh), an endothelium-dependent relaxing agent, and contraction induced by the thromboxane mimetic U-46619 were measured in ring segments of mesenteric and renal arteries from pregnant and nonpregnant guinea pigs. To determine the role of the endothelium, nitric oxide (NO), and vasodilator prostaglandins in modulating vascular response, rings were denuded, treated with N omega-nitro-L-arginine (L-NNA) to inhibit NO synthase, or treated with indomethacin to inhibit cyclooxygenase. Pregnancy increased ACh-stimulated relaxation of mesenteric arteries but not renal arteries. L-NNA significantly reduced ACh sensitivity (based on the concentration that produced 50% of the maximal response) in arteries from pregnant and nonpregnant animals, and indomethacin slightly decreased maximal relaxation only in the renal artery of nonpregnant animals. ACh sensitivity of mesenteric arteries was still increased after L-NNA or indomethacin. Pregnancy reduced the threshold concentration of U-46619 in mesenteric artery but had no effect on contraction of renal artery. Contraction of both arteries was enhanced by denudation. L-NNA and indomethacin were less effective than denudation in arteries from pregnant and nonpregnant animals, which suggests that pregnancy alters thromboxane contraction by endothelium-dependent mechanisms other than NO and prostaglandins. Thus, pregnancy differentially alters vascular reactivity of mesenteric and renal arteries in the guinea pig.

Regionalization of Endothelium-Dependent Relaxation in the Thoracic Aorta of Pregnant and Nonpregnant Guinea Pigs

“…This is similar to the effect of pregnancy on the uterine, mesenteric and carotid arteries [12][13][14], Thus, the effect of pregnancy on stimulated NO release is specific for receptor-mediated release rather than for an alteration in the ability of the endothelium to produce NO or the sensi tivity of the underlying smooth muscle to NO.…”

“…The mechanism by which pregnancy increases relax ation to ACh is apparently estradiol-dependent. Prior study has shown an increase in both basal and stimulated release of NO in some but not all vessel beds during preg nancy [12][13][14]. Calcium-dependent NO synthase activity is increased by pregnancy and these changes can be mim icked by estradiol administration and in the brain blocked by tamoxifen [15,16].…”

Oxytocin does not directly affect vascular tone in vessels from nonpregnant and pregnant rats

“…Pregnancy is a physiological state where vasodilation is necessary to accommodate a 40-50% increase in blood volume required to meet the oxygen and nutritional requirements of the growing uterus and developing fetuses (18,43). This is accompanied by an attenuated responsiveness of maternal vessels to pressor agents (17,29,30,39,40,45) and an enhanced response to vasodilators (28,31). The mechanisms underlying these vascular changes are not clearly understood.…”

Effects of Phytoestrogens on Acetylcholine- and Isoprenaline-Induced Vasodilation in Rat Aorta

“…High levels of circulating estrogen have been reported to modulate the vasoactive reagentsinduced responses. Acetylcholine (ACh)-induced endothelium-dependent vasodilations are increased during the late stage of pregnancy in guinea pig mesenteric artery (3) and rat aorta (4), and it has also been found in 17b-estradiol (E 2)-treated rat aorta (5) or rabbit femoral artery (6). Furthermore, we have reported that the relaxing response to isoprenaline (ISO) was suppressed by a short-term treatment with E2 in rat aorta (7).…”