This Article Full Text Full Text (PDF) All Versions of this Article: 45/2/193    most recent 01.HYP.0000153053.82032.bfv1 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hermann, M. Articles by Ruschitzka, F. Search for Related Content PubMed PubMed Citation Articles by Hermann, M. Articles by Ruschitzka, F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CELECOXIB SODIUM CHLORIDE Medline Plus Health Information High Blood Pressure Related Collections Cardio-renal physiology/pathophysiology Animal models of human disease Other hypertension Hypertension - basic studies

(Hypertension. 2005;45:193.)
© 2005 American Heart Association, Inc.

Scientific Contributions

Selective COX-2 Inhibitors and Renal Injury in Salt-Sensitive Hypertension

Matthias Hermann; Sidney Shaw; Eva Kiss; Giovanni Camici; Nico Bühler; Remy Chenevard; Thomas F. Lüscher; Hermann J. Gröne; Frank Ruschitzka

From Cardiovascular Research (M.H., G.C., N.B.), Physiology, University Zürich-Irchel, Switzerland; Cardiovascular Center (M.H., R.C., T.F.L., F.R.), Cardiology, University Hospital Zürich, Switzerland; Department of Clinical Research (S.S.), University Hospital Bern, Switzerland; German Cancer Research Center (DKFZ) (E.K., H.J.G.), Department of Cellular and Molecular Pathology, Heidelberg, Germany.

Correspondence to Frank Ruschitzka, MD, FESC, Cardiology, University Hospital Zürich, 8091 Zürich, Switzerland. E-mail frank.ruschitzka{at}usz.ch

In view of the ongoing controversy of cardiorenal safety of selective COX-2 inhibitors (coxibs), the present study was designed to examine the effects of 2 different coxibs, celecoxib and rofecoxib, compared with a traditional NSAID, diclofenac, and placebo on renal morphology and function in salt-sensitive hypertension. Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were fed with NaCl-enriched diet (4% NaCl) for 8 weeks. Diclofenac (DS-diclofenac), rofecoxib (DS-rofecoxib), celecoxib (DS-celecoxib), or placebo was added to chow from weeks 6 to 8. Immunostaining for monocytes/macrophages (ED1) and cytotoxic T lymphocytes (CD8) was performed. In addition, renal morphology and proteinuria were assessed. Renal cortex mRNA was isolated for determination of COX-2, eNOS, and CRP mRNA by real-time reverse-transcriptase polymerase chain reaction. Untreated hypertensive animals showed glomerular injury including collapsing glomerulopathy, mesangial sclerosis, mesangiolysis, extracapillary proliferation, protein drops, and an especially high grade of glomerulosclerosis (P<0.05 versus DR-placebo) and CD8-positive and ED1-positive cells (P<0.01 versus DR-placebo), which was improved by celecoxib but not by diclofenac and rofecoxib. C-reactive protein mRNA in renal cortex was increased in DS-placebo animals (P<0.05 versus DR-placebo) and normalized by celecoxib (P<0.05 versus DS-placebo), whereas eNOS mRNA was decreased in the DS-rofecoxib group (P<0.05 versus DR-placebo, DS-celecoxib, and DS-diclofenac). Proteinuria was observed in hypertensive animals (P<0.0001 versus DR-placebo), increased by rofecoxib (P<0.05 versus DS-placebo), and normalized by celecoxib (P=0.0015 versus DS-placebo). This head-to-head comparison of selective and nonselective COX inhibitors demonstrates differential effects of coxibs on renal morphology and function in salt-dependent hypertension.

Key Words: hypertension • kidney • proteinuria

This article has been cited by other articles:

				H. Cheng, X. Fan, Y. Guan, G. W. Moeckel, R. Zent, and R. C. Harris Distinct Roles for Basal and Induced COX-2 in Podocyte Injury J. Am. Soc. Nephrol., September 1, 2009; 20(9): 1953 - 1962. [Abstract] [Full Text] [PDF]

				L. Wang, P. J. Flannery, P. B. Rosenberg, T. A. Fields, and R. F. Spurney Gq-Dependent Signaling Upregulates COX2 in Glomerular Podocytes J. Am. Soc. Nephrol., November 1, 2008; 19(11): 2108 - 2118. [Abstract] [Full Text] [PDF]

				M. M. Diaz Encarnacion, G. M. Warner, C. E. Gray, J. Cheng, H. K. H. Keryakos, K. A. Nath, and J. P. Grande Signaling pathways modulated by fish oil in salt-sensitive hypertension Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1323 - F1335. [Abstract] [Full Text] [PDF]

				E. A. Jaimes, M.-S. Zhou, D. D. Pearse, L. Puzis, and L. Raij Upregulation of cortical COX-2 in salt-sensitive hypertension: role of angiotensin II and reactive oxygen species Am J Physiol Renal Physiol, February 1, 2008; 294(2): F385 - F392. [Abstract] [Full Text] [PDF]

				W. B. White Cardiovascular Effects of the Cyclooxygenase Inhibitors Hypertension, March 1, 2007; 49(3): 408 - 418. [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]

				A. Zhang, Z. Dong, and T. Yang Prostaglandin D2 inhibits TGF-beta1-induced epithelial-to-mesenchymal transition in MDCK cells Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1332 - F1342. [Abstract] [Full Text] [PDF]

				J. Zhang, E. L. Ding, and Y. Song Adverse Effects of Cyclooxygenase 2 Inhibitors on Renal and Arrhythmia Events: Meta-analysis of Randomized Trials JAMA, October 4, 2006; 296(13): 1619 - 1632. [Abstract] [Full Text] [PDF]

				M. Albaqumi, T. J. Soos, L. Barisoni, and P. J. Nelson Collapsing Glomerulopathy J. Am. Soc. Nephrol., October 1, 2006; 17(10): 2854 - 2863. [Abstract] [Full Text] [PDF]

				M. Hermann and F. Ruschitzka Novel anti-inflammatory drugs in hypertension Nephrol. Dial. Transplant., April 1, 2006; 21(4): 859 - 864. [Full Text] [PDF]

				L. Barisoni, M. P. Madaio, M. Eraso, D. L. Gasser, and P. J. Nelson The kd/kd Mouse Is a Model of Collapsing Glomerulopathy J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2847 - 2851. [Abstract] [Full Text] [PDF]

				M. Hermann, H. Krum, and F. Ruschitzka To the Heart of the Matter: Coxibs, Smoking, and Cardiovascular Risk Circulation, August 16, 2005; 112(7): 941 - 945. [Full Text] [PDF]

				J. Adams, E. Kiss, A. B.V. Arroyo, M. Bonrouhi, Q. Sun, Z. Li, N. Gretz, A. Schnitger, C. C. Zouboulis, M. Wiesel, et al. 13-cis Retinoic Acid Inhibits Development and Progression of Chronic Allograft Nephropathy Am. J. Pathol., July 1, 2005; 167(1): 285 - 298. [Abstract] [Full Text] [PDF]

				I. J. Chang and R. C. Harris Are All COX-2 Inhibitors Created Equal? Hypertension, February 1, 2005; 45(2): 178 - 180. [Full Text] [PDF]