Effects of Pregnancy, Hypertension and Nitric Oxide Inhibition on Rat Uterine Artery Myogenic Reactivity

Background/Aims: The purpose of this study was to examine the effects of hypertension and nitric oxide (NO) inhibition on myogenic tone in uterine arteries during pregnancy. Methods: Premyometrial radial uterine arteries from nonpregnant and late pregnant Sprague-Dawley rats were evaluated for myogenic reactivity from the following groups: control, hypertensive/NO-inhibited ( L -NAME treatment) and normotensive/NO-inhibited ( L -NAME plus hydralazine). Results: In both nonpregnant and pregnant animals, L -NAME treatment significantly elevated blood pressures, while the addition of hydralazine made the animals normotensive. In nonpregnant animals, little myogenic tone was seen in controls; tone increased significantly in the L -NAME group, and was attenuated in those treated with L -NAME plus hydralazine. In pregnant animals, controls developed significant tone; this was reduced in the L -NAME group, and returned to control levels in the L -NAME plus hydralazine group. Conclusions: Dimensional measurements showed that arteries from the pregnant hypertensive group did not undergo expansive remodeling, suggesting that tone development is related to phenotypic alterations in vascular smooth muscle Received: September 15, 2009 Accepted after revision: November 11, 2009 Published online: April 30, 2010 Dr. George Osol Department of Obstetrics, Gynecology, and Reproductive Medicine University of Vermont College of Medicine C-217A Given Building, Burlington, VT 05405 (USA) Tel. +1 802 656 1203, Fax +1 802 656 8771, E-Mail gosol @ uvm.edu © 2010 S. Karger AG, Basel Accessible online at: www.karger.com/jvr D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /2 2/ 20 17 7 :1 3: 11 P M Barron /Mandala /Osol J Vasc Res 2010;47:463–471 464 [1, 8, 9] that allows for successful pregnancy outcome. In uterine vessels, outward expansive remodeling is seen (increased lumen diameter and unchanged wall thickness) [10, 11] , which serves to reduce uterine vascular resistance in normal pregnancy [4, 12] . Conversely, in chronic hypertensive states, this process is reversed, with inward remodeling (decreased lumen diameter and increased wall thickness) [12, 13] leading to a marked increase in peripheral vascular resistance [3, 9] . In preeclamptic women, the interaction between gestation and hypertension results in an attenuated outward remodeling process [11] , and placental underperfusion and endothelial dysfunction [14] . While structural gestational remodeling is a key factor in allowing for adequate increases in uterine blood flow, under physiological conditions, vascular resistance is determined by the combination of passive resistance artery structure and the ambient level of constriction, or tone. Myogenic tone – the intrinsic ability of smooth muscle to sustain constriction in response to intravascular pressure – is absent in uterine radial arteries from nonpregnant animals, yet appears in those same types of arteries in late pregnancy [15–17] . The objective of this study was to evaluate the effects of hypertension and nitric oxide (NO) inhibition on myogenic tone in pregnancy, as the ability of a vessel to constrict and dilate in response to changes in pressure plays a key role in regulating blood flow to the uterus. Our working hypothesis was that the level of tone would be directly related to hypertension and that treatment with L -NAME would cause increases in tone while co-treatment with hydralazine would cause a return to control levels of tone in both nonpregnant and late pregnant groups. Hydralazine was co-administered with L -NAME to normalize blood pressure and thereby dissociate the effects of elevated pressure from those of NO inhibition, as hydralazine is a widely used treatment for hypertension in pregnancy [2, 18, 19] . The results support this hypothesis in the nonpregnant state. During pregnancy, however, the data suggest that changes in tone may be primarily related to the degree of expansive remodeling, which appears to be mediated by both NO and intravascular pressure.