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      Renal Medullary Infusion of Indomethacin and Adenosine

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          Abstract

          Perfusion of the renal medulla and osmotic hypertonicity of its interstitium are the two important features of this zone which can influence body fluid homeostasis, especially arterial blood pressure. Separate manipulation of the two variables is best obtained with the intramedullary infusion of active agents. In this study, a set-up combining the possibility of infusion into the medulla with measurement of local blood flow (MBF, laser-Doppler flux) and extracellular ion concentration (tissue electrical admittance, Y) was used to determine effects of intramedullary indomethacin (Indo) and adenosine (Ado) in anaesthetized rats. Intramedullary Indo, 1 mg kg<sup>–1 </sup>h<sup>–1</sup>, significantly increased tissue Y, by 12 ± 3%, and significantly decreased MBF by 20 ± 3%.There was also an unexplained increase of sodium excretion (U<sub>Na</sub>V) by 169 ± 24% and of urine flow (V) by 62 ± 6% (n = 10, both p < 0.03). Intramedullary Ado, 5 µg kg<sup>–1</sup> h<sup>–1</sup>, did not alter Y, MBF or U<sub>Na</sub>V, whereas V increased 45 ± 6% and urine osmolality decreased 25 ± 4% (both changes significant). Elevation of medullary interstitial Ado to a level that did not alter MBF or U<sub>Na</sub>V induced a moderate defect of urine concentration that was not due to a decrease in ionic medullary hypertonicity.

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          Most cited references 5

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          Cytochrome P450 metabolites of arachidonic acid in the control of renal function.

           K G Maier,  R J Roman (2001)
          Recent studies indicate that arachidonic acid is primarily metabolized by cytochrome P450 enzymes of the 4A and 2C families in the kidney to 20-hydroxyeicosatetraenoic acid (HETE), epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids. These compounds play central roles in the regulation of renal tubular and vascular function. 20-HETE is produced by renal vascular smooth muscle (VSM) cells and is a potent constrictor that depolarizes VSM cells by blocking the calcium-activated potassium channel. Inhibition of the formation of 20-HETE blocks the myogenic response of isolated renal arterioles in vitro, and autoregulation of renal blood flow and tubuloglomerular feedback responses in vivo. EETs are products formed in the endothelium and are potent dilators that activate the calcium-activated potassium channel in renal VSM. Endothelial-dependent vasodilators stimulate the release of EETs, and these compounds appear to serve as an endothelial-derived hyperpolarizing factor. EETs and 20-HETE are produced in the proximal tubule. There, they regulate sodium/potassium-ATPase activity and serve as second messengers for the natriuretic effects of dopamine, parathyroid hormone and angiotensin II. 20-HETE is also produced in the thick ascending loop of Henle. It regulates sodium-potassium-chloride transport in this nephron segment. The renal production of cytochrome P450 metabolites of arachidonic acid is altered in hypertension, diabetes, toxemia of pregnancy, and hepatorenal syndrome. Given the importance of cytochrome P450 metabolites of arachidonic acid in the control of renal function, it is likely that changes in this system contribute to the abnormalities in renal function that are associated with many of these conditions.
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            Prostaglandin E2 induced changes in renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat

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              Osmotic hypertonicity of the renal medulla during changes in renal perfusion pressure in the rat

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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2004
                July 2004
                02 February 2004
                : 27
                : 1
                : 29-34
                Affiliations
                Laboratory of Renal and Body Fluid Physiology, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
                Article
                75620 Kidney Blood Press Res 2004;27:29–34
                10.1159/000075620
                14679312
                © 2004 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: 3, References: 27, Pages: 6
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/75620
                Categories
                Original Paper

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