Stimulated nitric oxide release and nitric oxide sensitivity in forearm arterial vasculature during normotensive and preeclamptic pregnancy,☆☆,

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Abstract

Objective: We sought to determine whether the enhanced forearm vascular activity of nitric oxide during pregnancy and preeclampsia is associated with altered smooth muscle sensitivity to nitric oxide or with stimulated nitric oxide release. Study Design: Forearm blood flow responses to brachial artery infusion of glyceryl trinitrate (a nitric oxide donor), serotonin (an endothelium-dependent nitric oxide–mediated agonist), and ritodrine (a β-adrenergic receptor agonist) were studied in 10 nonpregnant women, 12 pregnant women, and 7 women with preeclampsia by means of strain-gauge plethysmography. Responses to each drug (maximum dilator response and the sum of the percentage of dilator responses to each drug) were compared by analysis of variance. Results: Compared with nonpregnant women, pregnant subjects showed reduced responses to serotonin (summary response, 117 ± 19 vs 221 ± 30; P < .05). Responses to serotonin were reduced in the group with preeclampsia compared with those in the nonpregnant group (summary response, 71 ± 28; P < .05) but did not differ from the responses in pregnant women. There were no differences between responses to glyceryl trinitrate and responses to ritodrine in any of the groups. Conclusion: Vascular smooth muscle sensitivity to nitric oxide is not altered in normal pregnancy or preeclampsia, but dilator responses to serotonin appear blunted. Alterations in serotonin receptor coupling to nitric oxide synthase, or a limitation of availability of the substrate for nitric oxide synthase (L -arginine) during pregnancy, could account for the reduction in stimulated nitric oxide release. (Am J Obstet Gynecol 1999;181:1479-85.)

Section snippets

Subjects

Twelve healthy primiparous women, 7 primiparous women with preeclampsia who had not received antihypertensive therapy, and 10 healthy nonpregnant women who were not receiving hormonal contraception were studied (Table I). Subjects were nonsmokers and refrained from alcohol and caffeine for a minimum of 4 hours before each study. Women with preeclampsia had persistently elevated blood pressure readings of at least 140 mm Hg systolic, and 90 mm Hg diastolic; proteinuria (≥300 mg protein in 24

Results

Compared with nonpregnant subjects, pregnant subjects had reduced forearm vascular resistance but similar systemic blood pressure. Systemic blood pressure and forearm vascular resistance were higher in subjects with preeclampsia than in pregnant subjects. Forearm volume and length did not differ between the study groups. Forearm blood flow did not vary significantly in the noninfused arm in any of the groups during the study. Blood pressure did not vary significantly within the time course of

Comment

This is the first study to determine vasodilator responses in the human forearm during pregnancy. The results demonstrate that vascular smooth muscle sensitivity to nitric oxide is not altered in normal pregnancy or preeclampsia. Thus gestation-related increases in vascular nitric oxide activity are most likely mediated by increased endothelial nitric oxide production. An unexpected finding of our study was that dilator responses to serotonin appear blunted during both normotensive and

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    Supported by Wellbeing, the health research charity for women and children.

    ☆☆

    Reprint requests: Stephen C. Robson, MD, Department of Obstetrics and Gynaecology, University of Newcastle upon Tyne, Fourth Floor, Leaze’s Wing, Royal Victoria Infirmary, Queen Victoria Rd, Newcastle upon Tyne, United Kingdom NE1 4LP.

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