+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

      Effect of High-Salt Diet on Vascular Relaxation and Oxidative Stress in Mesenteric Resistance Arteries


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          This study tested the hypothesis that superoxide levels are elevated in isolated mesenteric resistance arteries (100–300 µm) from rats fed a short-term high-salt (HS) diet (4% NaCl for 3 days) compared to controls fed a low-salt (LS) diet (0.4% NaCl). Vascular relaxation induced by the superoxide dismutase mimetic tempol (4-hydroxytetramethylpiperidine-1-oxyl), the NADPH oxidase inhibitor apocynin and the xanthine/xanthine oxidase inhibitor oxypurinol was significantly larger in mesenteric arteries from animals fed HS diet compared to arteries from animals fed LS diet. Basal superoxide levels assessed via dihydroethidine (DHE) fluorescence were significantly elevated in arteries from rats fed HS diet, and were reduced by tempol, apocynin and oxypurinol, but not by L-NAME. Basal and methacholine-induced NO production (assessed by DAF-2T fluorescence) was significantly reduced in arteries from rats fed HS diet versus arteries from rats on LS diet. Impaired methacholine-induced NO release and vascular relaxation were restored by tempol and apocynin, but not by oxypurinol. These data suggest that the elevated production of superoxide by NADPH oxidase and xanthine/xanthine oxidase contribute to elevated basal superoxide levels, reduced NO release and impaired vascular relaxation in mesenteric resistance arteries of rats fed HS diet.

          Related collections

          Most cited references 6

          • Record: found
          • Abstract: not found
          • Article: not found

          Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension

            • Record: found
            • Abstract: found
            • Article: not found

            20-HETE-induced contraction of small coronary arteries depends on the activation of Rho-kinase.

            20-HETE is a potent constrictor of small blood vessels and has been suggested to play a crucial role in the generation of myogenic tone and the development of hypertension. In the present study, we investigated the mechanisms by which exogenously applied 20-HETE modulates vascular tone in small porcine coronary arteries. In organ chamber experiments, 20-HETE elicited a concentration-dependent contraction of small porcine coronary artery rings that was partially inhibited by the cyclooxygenase inhibitor diclofenac, the thromboxane and endoperoxide receptor antagonist SQ29548, and the thromboxane A2 synthase inhibitor furegrelate. Removal of endothelium attenuated the response to 20-HETE, whereas preconstriction of endothelium-denuded vessels to 25% of the maximum response with KCl markedly enhanced the response to 20-HETE. This 20-HETE-induced contraction was not associated with a significant increase in the intracellular concentration of Ca2+. 20-HETE-induced contraction was also observed in beta-escin-permeabilized arteries precontracted with a submaximal concentration of Ca2+ and was abolished by the Rho-kinase inhibitor Y27632, but was insensitive to the PKC inhibitor RO 31-8220. 20-HETE elicited the phosphorylation of the myosin light chain (MLC20) in coronary artery rings, an effect that was sensitive to Y27632 and mimicked by the thromboxane analog U46619. These data suggest that in small porcine coronary arteries, 20-HETE can induce contraction by 2 mechanisms, one endothelium-dependent involving the cyclooxygenase-dependent generation of vasoconstrictor prostanoids, and the other endothelium-independent. The latter response is associated with the activation of Rho-kinase, phosphorylation of MLC20, and sensitization of the contractile apparatus to Ca2+.
              • Record: found
              • Abstract: found
              • Article: not found

              Renal cytochrome P450 omega-hydroxylase and epoxygenase activity are differentially modified by nitric oxide and sodium chloride.

              Renal function is perturbed by inhibition of nitric oxide synthase (NOS). To probe the basis of this effect, we characterized the effects of nitric oxide (NO), a known suppressor of cytochrome P450 (CYP) enzymes, on metabolism of arachidonic acid (AA), the expression of omega-hydroxylase, and the efflux of 20-hydroxyeicosatetraenoic acid (20-HETE) from the isolated kidney. The capacity to convert [(14)C]AA to HETEs and epoxides (EETs) was greater in cortical microsomes than in medullary microsomes. Sodium nitroprusside (10-100 microM), an NO donor, inhibited renal microsomal conversion of [(14)C]AA to HETEs and EETs in a dose-dependent manner. 8-bromo cGMP (100 microM), the cell-permeable analogue of cGMP, did not affect conversion of [(14)C]AA. Inhibition of NOS with N(omega)-nitro-L-arginine-methyl ester (L-NAME) significantly increased conversion of [(14)C]AA to HETE and greatly increased the expression of omega-hydroxylase protein, but this treatment had only a modest effect on epoxygenase activity. L-NAME induced a 4-fold increase in renal efflux of 20-HETE, as did L-nitroarginine. Oral treatment with 2% sodium chloride (NaCl) for 7 days increased renal epoxygenase activity, both in the cortex and the medulla. In contrast, cortical omega-hydroxylase activity was reduced by treatment with 2% NaCl. Coadministration of L-NAME and 2% NaCl decreased conversion of [(14)C]AA to HETEs without affecting epoxygenase activity. Thus, inhibition of NOS increased omega-hydroxylase activity, CYP4A expression, and renal efflux of 20-HETE, whereas 2% NaCl stimulated epoxygenase activity.

                Author and article information

                J Vasc Res
                Journal of Vascular Research
                S. Karger AG
                August 2007
                18 May 2007
                : 44
                : 5
                : 382-390
                Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisc., USA
                102955 J Vasc Res 2007;44:382–390
                © 2007 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: 6, References: 21, Pages: 9
                Research Paper


                Comment on this article