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      An Intron 4 Gene Polymorphism in Endothelial Cell Nitric Oxide Synthase Might Modulate Volume-Dependent Hypertension in Patients on Hemodialysis

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          Abstract

          Nitric oxide (NO) has some relevance to the pathophysiology of hypertension. We examined the distribution of endothelial nitric oxide synthase (ecNOS4) gene polymorphism in patients with essential hypertension (n = 107) in comparison with healthy subjects (n = 362), and then studied the possibility that ecNOS4 gene polymorphism affects changes in blood pressure (BP) due to water load in hemodialysis patients. Though the NO metabolite (NOx) level in subjects with the a allele (31.2 ± 1.76 µmol/l) was significantly lower than in those without the a allele (35.6 ± 0.90 µmol/l) (p = 0.0263), we found no association between this gene polymorphism and essential hypertension. However, there still remains the possibility that the NO response to elevation of BP might be suppressed in patients with hypertension. In order to examine the association between ecNOS4 gene polymorphism and volume-dependent hypertension, 181 hemodialysis patients with complete anuria were recruited. Depending on the increase in mean BP (mm Hg) divided by percent increase in body weight (ΔBP/ΔBW), patients were divided into high responders (High-R: ΔBP/ΔBW >2.0 mm Hg; n = 90) and low responders (Low-R: ΔBP/ΔBW <2.0 mm Hg; n = 91). In the High-R group, the frequencies of a/a, b/a and b/b genotypes were 1.1, 32.1 and 66.8%, respectively, and in the Low-R group, these frequencies were 1.1, 9.4 and 89.5%, respectively. The relative risk for those in the High-R group conferred by the ecNOS4 a allele ( b/a + a/a) was 3.64 (95% confidence intervals: 1.60–8.24, p = 0.0089). This study did not show a strong involvement of ecNOS4 gene polymorphism, at least in the basal NO production in patients with essential hypertension, however, it indicated that ecNOS4 gene polymorphism might modulate changes in BP due to water load in patients on hemodialysis, thus indicating that these polymorphisms may be involved in the pathophysiology of volume-dependent hypertension.

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          Most cited references 3

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          NO at work

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            High Accumulation of Endothelial Nitric Oxide Synthase (ecNOS):A Gene Polymorphism in Patients with End-Stage Renal Disease

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              Activation of Nitric Oxide Synthesis in Vascular Smooth Muscle Cells and Macrophages During Development in Spontaneously Hypertensive Rats

               X JIN (1996)
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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                2000
                July 2000
                21 June 2000
                : 85
                : 3
                : 232-237
                Affiliations
                aInternal Medicine II, Jikei University School of Medicine; bDepartment of Clinical Chemistry, and cKidney Center, Toranomon Hospital, Tokyo, Japan
                Article
                45666 Nephron 2000;85:232–237
                10.1159/000045666
                10867538
                © 2000 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 2, Tables: 4, References: 22, Pages: 6
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/45666
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