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      Photorelaxation Is Not Attenuated by Inhibition of the Nitric Oxide-cGMP Pathway

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          Abstract

          Photorelaxation of arteries by ultraviolet (UV) light is hypothesized to result from nitric oxide (NO) released from photoactivable stores. Recently, a study reported enhanced photorelaxation of aortic tissue from rats administered the NO synthase (NOS) inhibitor N<sup>ω</sup>-nitro- L-arginine ( L-NNA). Presumably, the potentiated photorelaxation was due to NO generated from UV-light-induced decomposition of the NO<sub>2</sub> moiety of L-NNA. However, we hypothesized that photorelaxation is: (1) not the result of NO synthesis and subsequent activation of guanylate cyclase and (2) not due to hyperpolarization induced by NO or any other factor. Endothelium-denuded rat aortic rings were suspended in isolated baths for isometric force measurement. Rings were exposed to UV light (366 nm) before addition of phenylephrine or KCI, and then at each agonist concentration during a cumulative concentration response curve. NOS inhibition by L-NNA and L-thiocitrulline, which lacks an NO<sub>2</sub> group, enhanced photorelaxation of basal myogenic tone and contraction to phenylephrine (EC70). Furthermore, relaxation of a maximum phenylephrine-induced contraction to the NO donor S-nitroso-N-acetyl-D L-penicillamine during UV light exposure was not altered by incubation of rings with L-NNA or tissues from animals fed L-NNA. These data demonstrate that NO is not produced endogenously or from the breakdown of L-NNA to result in photorelaxation. Methylene blue (MB) did not alter photorelaxation, suggesting that cGMP is not essential to the response. MB and L-NNA together potentiated photorelaxation of basal myogenic tone and phenylephrine-induced contraction. Photorelaxation of KCl-induced contraction was unaltered, indicating that hyperpolarization does not contribute to the relaxation. Photorelaxation of basal myogenic tone and KCl-induced contraction excludes the possibility that UV light is interfering with agonist-receptor binding. Collectively, these results refute the hypotheses that photorelaxation results from activation of the NO-cGMP pathway, release of a hyperpolarization factor, or inhibition of drug-receptor interaction. Interestingly, photorelaxation may be inhibited by NO-cGMP pathway activation, uncovering a novel effect of this messenger system on vascular reactivity.

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          Author and article information

          Journal
          JVR
          J Vasc Res
          10.1159/issn.1018-1172
          Journal of Vascular Research
          S. Karger AG
          1018-1172
          1423-0135
          1996
          1996
          24 September 2008
          : 33
          : 4
          : 299-307
          Affiliations
          Department of Physiology, The University of Michigan, Ann Arbor, Mich., USA
          Article
          159157 J Vasc Res 1996;33:299–307
          10.1159/000159157
          8695754
          © 1996 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
          Pages: 9
          Categories
          Research Paper

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