HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/2/F368    most recent 00500.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Yao, B. Articles by Zhang, M.-Z. Search for Related Content PubMed PubMed Citation Articles by Yao, B. Articles by Zhang, M.-Z.

Role of renal cortical cyclooxygenase-2 expression in hyperfiltration in rats with high-protein intake

Division of Nephrology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee

Submitted 13 December 2005 ; accepted in final form 15 March 2006

Renal cortical cyclooxygenase-2 (COX-2) is restricted to the macula densa and adjacent cortical thick ascending limbs (MD/cTALH). Renal cortical COX-2 increases in response to diabetes and renal ablation, both of which are characterized by hyperfiltration and reduced NaCl delivery to the MD due to increased proximal NaCl reabsorption. High-protein intake also induces hyperfiltration and decreases NaCl delivery to the MD due to increased NaCl reabsorption proximally. We investigated whether high protein induces cortical COX-2 and whether cortical COX-2 contributes to high protein-induced hyperfiltration and increased intrarenal renin biosynthesis. Cortical COX-2 increased after protein loading but decreased after protein restriction. COX-2 inhibition attenuated high protein-induced hyperfiltration but had no effect on high protein-induced intrarenal renin elevation. Therefore, induction of cortical COX-2 contributed to high protein-induced hyperfiltration but not intrarenal renin elevation. In the kidney cortex, neuronal nitric oxide synthase (nNOS) is also localized to the MD, and interactions between intrarenal nNOS and COX-2 systems have been proposed. Cortical COX-2 elevation seen in salt restriction was blocked by nNOS inhibiton. Cortical nNOS expression also increased after protein loading, and inhibition of nNOS activity completely reversed high protein-induced cortical COX-2 elevation and hyperfiltration. These results indicate that NO is a mediator of high protein-induced cortical COX-2 elevation and suggest that both intrarenal nNOS and COX-2 systems appear to regulate afferent arteriolar tone and subsequent hyperfiltration seen in high-protein intake.

prostaglandin synthase G₂/H₂; glomerular filtration rate; protein diet

This article has been cited by other articles:

				D. Z. I. Cherney, J. W. Scholey, R. Nasrallah, M. G. Dekker, C. Slorach, T. J. Bradley, R. L. Hebert, E. B. Sochett, and J. A. Miller Renal hemodynamic effect of cyclooxygenase 2 inhibition in young men and women with uncomplicated type 1 diabetes mellitus Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1336 - F1341. [Abstract] [Full Text] [PDF]

				D. Z.I. Cherney, J. A. Miller, J. W. Scholey, T. J. Bradley, C. Slorach, J. R. Curtis, M. G. Dekker, R. Nasrallah, R. L. Hebert, and E. B. Sochett The Effect of Cyclooxygenase-2 Inhibition on Renal Hemodynamic Function in Humans With Type 1 Diabetes Diabetes, March 1, 2008; 57(3): 688 - 695. [Abstract] [Full Text] [PDF]

				H. Cheng, S. Wang, Y.-I. Jo, C.-M. Hao, M. Zhang, X. Fan, C. Kennedy, M. D. Breyer, G. W. Moeckel, and R. C. Harris Overexpression of Cyclooxygenase-2 Predisposes to Podocyte Injury J. Am. Soc. Nephrol., February 1, 2007; 18(2): 551 - 559. [Abstract] [Full Text] [PDF]