Fenoldopam Improves Corticomedullary Oxygen Delivery and Attenuates Angiogenesis Gene Expression in Acute Ischemic Renal Injury

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.

Abstract

Background/Aims: Vasoactive compounds are known to affect intrarenal hemodynamics and gene transcription, but specific effects of fenoldopam in the setting of acute renal ischemia are not known. We utilized a rat model of acute ischemic nephropathy to test the hypothesis that fenoldopam improves corticomedullary tissue oxygen tension (PtO2) and attenuates angiogenesis gene expression in acute renal ischemia. Methods: Rats anesthetized with 50 mg/kg urethane were divided into 4 groups (n = 6 each): (1) sham with infusion of 0.9% saline; (2) sham with infusion of 0.1 µg·kg–1·min–1 fenoldopam; (3) unilateral renal ischemia followed by 6 h of reperfusion with saline, and (4) ischemia/reperfusion with fenoldopam. Renal artery blood flow (RBF), renal cortical perfusion (RCP), and PtO2 were recorded throughout. Total RNA from left kidneys was used to probe microarrays. Gene expression was measured as percent positive control (GAPDH) and confirmed using RT-PCR. Results: Fenoldopam significantly increased RBF (p < 0.05), RCP (p < 0.01) and PtO2 (p <0.01) in both non-ischemic and post-ischemic kidneys. Fenoldopam attenuated 11 of the 13 ischemia-induced genes and 44 of 78 ischemia-suppressed genes. This attenuation was statistically significant (p <0.05) for five genes. Conclusion: Data from this rat model of ischemic nephropathy suggest that fenoldopam improves intrarenal hemodynamics and attenuates ischemia-related changes in angiogenesis gene expression.

Related collections

Most cited references 21

Record: found
Abstract: found
Article: not found

Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal function in postischemic acute renal failure.

H Humes, D A Cieslinski, Lúcia M. C. Galvão … (1989)

To determine the timing and location of renal cell regeneration after ischemic injury to the kidney and to assess whether exogenous epidermal growth factor (EGF) enhances this regenerative repair process to accelerate recovery of renal function, experiments were undertaken in rats undergoing 30 min of bilateral renal artery clamp ischemia followed by reperfusion for varying time intervals. Renal cell regeneration, as reflected by incorporation of radiolabeled thymidine within the kidney, began between 24 to 48 h and reached a peak at 72 h after renal ischemia. As demonstrated by histoautoradiography, renal thymidine incorporation was essentially confined to tubule cells. Morphometric analysis of histoautoradiograph sections of renal tissue demonstrated that the majority of labeled cells were found in renal cortex, but some labeled cells were also located in the inner stripe of the outer medulla, suggesting that injury to medullary thick ascending limbs also occurs in this ischemic model. Exogenous EGF administration produced increases in renal thymidine incorporation compared with non-treated animals at 24, 48, and 72 h after ischemic injury. This accelerated DNA replicative process was associated with significantly lower peak blood urea nitrogen (BUN) and serum creatinine levels, averaging 63 +/- 20 and 3.1 +/- 0.4 mg/dl in EGF-treated ischemic rats compared with 149 +/- 20 and 5.1 +/- 0.1 mg/dl, respectively, in nontreated ischemic rats, and was also associated with a return to near normal BUN and serum creatinine levels in EGF-treated animals approximately 4 d earlier than that observed in nontreated animals. This report is the first demonstration that EGF accelerates the repair process of a visceral organ after an injurious insult.

0 comments Cited 52 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Thrombospondin-1 is a major activator of TGF-beta in fibrotic renal disease in the rat in vivo.

Henry Krutzsch, Lynne Roberts, J. Ullrich … (2004)

Transforming growth factor-beta (TGF-beta), a profibrotic cytokine involved in many scarring processes, has to be activated extracellularly before it can bind to its receptors. Thrombospondin 1 (TSP1), a multifunctional matricellular glycoprotein, has been identified as an activator of TGF-beta in in vitro systems and during mouse postnatal development in vivo. TSP1 is expressed de novo in many inflammatory disease processes, including glomerular disease. In this study we investigated whether peptides specifically interfering with the activation process of TGF-beta by TSP1 may be able to block activation of TGF-beta in an in vivo model of mesangial proliferative glomerulonephritis. Continuous intravenous infusion of blocking peptide by minipumps significantly reduced expression of active TGF-beta in glomeruli on day 7 of disease as indicated by immunohistochemistry, bioassay, and activation of the TGF-beta signal transduction pathway, while total TGF-beta expression was unchanged. Inhibition of glomerular TGF-beta activation was accompanied by a decrease of glomerular extracellular matrix accumulation and proteinuria, but was without effect on mesangial cell proliferation or influx of monocytes/macrophages. TSP1 is a major endogenous activator of TGF-beta in experimental inflammatory glomerular disease. Drugs interfering with the activation of TGF-beta by locally produced TSP1 may be considered as a future specific treatment of scarring kidney disease.

0 comments Cited 37 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Regulation of endothelial matrix metalloproteinase-2 by hypoxia/reoxygenation.

Yaara Ben-Yosef, Nitza Lahat, Sarah M. Shapiro … (2002)

Among the consequences resulting from the exposure of endothelial cells (ECs) to ischemia/reperfusion is angiogenesis, involving degradation of vascular basement membrane and extracellular matrix. Matrix metalloproteinase (MMP)-2, a member of the MMP family, partakes in this process. MMP-2, secreted as a proenzyme, undergoes activation through interaction with membrane type (MT)1-MMP and the endogenous tissue inhibitor of MMPs (TIMP)-2. Although hypoxia and reoxygenation (H/R) are major constituents of ischemia/reperfusion processes, their direct effects on endothelial MMP-2 have been scarcely investigated. This study examined the in vitro effects of H/R on human macrovascular ECs (EAhy 926). The level of MMP-2 mRNA (Northern blot) and protein (zymography, ELISA) and the mRNA of its activator (MT1-MMP) and inhibitor (TIMP-2) were analyzed. Short (6-hour) hypoxia inhibited the mRNA expression of MMP-2, MT1-MMP, and TIMP-2, culminating in reduced latent and active MMP-2 protein. Prolonged (24-hour) hypoxia further suppressed MT1-MMP and TIMP-2 mRNA, whereas it enhanced MMP-2 mRNA and enzyme secretion (after 48-hour hypoxia). Reoxygenation did not influence the inhibited TIMP-2 but upregulated MMP-2 and MT1-MMP mRNA expression, leading to enhanced secretion of active MMP-2 protein. These results demonstrate H/R-mediated modulation of EC MMP-2 at both transcriptional and posttranscriptional levels. Prolonged hypoxia of ECs appears to enhance MMP-2 production and secretion, whereas reoxygenation further increases its level. These H/R-mediated effects on MMPs have the potential of enabling EC migration and possible angiogenesis.

0 comments Cited 35 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (publisher-id): KBR

Journal ID (nlm-ta): Kidney Blood Press Res

Journal ID (doi): 10.1159/issn.1420-4096

Title: Kidney and Blood Pressure Research

Publisher: S. Karger AG

ISSN (Print): 1420-4096

ISSN (Electronic): 1423-0143

Publication date Subscription-year: 2006

Publication date (Print): October 2006

Publication date (Electronic): 06 October 2006

Volume: 29

Issue: 3

Pages: 165-174

Affiliations

^aDivision of Anesthesiology and Critical Care, and ^bDepartment of Internal Medicine, University of Texas M.D. Anderson Cancer Center, Houston, Tex., and ^cDivision of Cardiothoracic Anesthesia and Critical Care Medicine, Duke University Medical Center, Durham, N.C., USA

Article

Publisher ID: 95350 Other ID: Kidney Blood Press Res 2006;29:165–174

DOI: 10.1159/000095350

PubMed ID: 16931895

SO-VID: 5c8169de-2d2a-407a-ba89-a00bffe1cd3b

License:

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.

History

Date received : 27 December 2005

Date accepted : 07 July 2006

Page count

Figures: 4, Tables: 1, References: 35, Pages: 10

Comments

Comment on this article

scite_

Cited by 6

See all cited by

Most referenced authors 338

See all reference authors

- Version 1

Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

Submit here before July 31, 2024

Fenoldopam Improves Corticomedullary Oxygen Delivery and Attenuates Angiogenesis Gene Expression in Acute Ischemic Renal Injury

Read this article at

Abstract

Related collections

Karger: Nephrology

Most cited references 21

Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal function in postischemic acute renal failure.

Thrombospondin-1 is a major activator of TGF-beta in fibrotic renal disease in the rat in vivo.

Regulation of endothelial matrix metalloproteinase-2 by hypoxia/reoxygenation.

Author and article information

Journal

Affiliations

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 249

Cited by 6

Most referenced authors 338