This Article Full Text Full Text (PDF) 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 Sanchez, P. L. Articles by Escalante, B. Search for Related Content PubMed PubMed Citation Articles by Sanchez, P. L. Articles by Escalante, B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB INDOMETHACIN Medline Plus Health Information Kidney Failure

(Hypertension. 1999;34:848-853.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Effect of Cyclooxygenase-2 Inhibition on Renal Function After Renal Ablation

Pedro Lopez Sanchez; Luis Miguel Salgado; Nicholas R. Ferreri; Bruno Escalante

From the Departments of Pharmacology and Toxicology (P.L.S.), Biochemistry (L.M.S.), and Molecular Biomedicine (B.E.), Centro de Investigacion y Estudios Avanzados del IPN; Escuela Superior Medicina IPN (P.L.S.), Mexico DF, Mexico; and Department of Pharmacology (N.R.F.), New York Medical College, Valhalla, NY.

Correspondence to Pedro Lopez, MD, Department of Pharmacology and Toxicology, Centro de Investigacion y Estudios Avanzados del IPN, Avenida Instituto Politecnico Nacional 2508, Mexico DF, CP 07300, Mexico. E-mail plopez{at}df1.telmex.net.mx

Abstract—Kidney failure is the common end of hypertension and renal diseases. Several authors have suggested that vasodilatory prostaglandins participate in the hemodynamic mechanism responsible for the development of kidney failure. However, the mechanism by which prostaglandins are increased in renal disease is not clear. Recently, 2 isoforms of the enzyme responsible for prostaglandin synthesis, cyclooxygenase, have been described as cyclooxygenase-1 (COX-1), a constitutive isoform, and cyclooxygenase-2 (COX-2), an inducible isoform. In the present study, we investigated whether COX-2–dependent prostaglandins participate in the evolution of renal functional changes after renal ablation. We inhibited prostaglandin synthesis by COX-1 and COX-2 with indomethacin (3 mg/kg) and prostaglandin synthesis by COX-2 with NS-398 (3 mg/kg) and tested the effect of these inhibitors on the renal functional changes elicited by renal ablation. Renal ablation produced an increase in urinary volume, protein, and prostaglandin E₂, whereas urinary sodium and potassium were not affected and urinary osmolarity decreased; treatment with indomethacin or NS-398 partially prevented the renal functional changes elicited by renal ablation. Immunoblots for COX showed an increase in the expression of COX-2 protein 2 days after renal ablation. Furthermore, COX-2 mRNA expression was increased 1 day after renal ablation. These data suggest that COX-2–dependent prostaglandins participate in the renal mechanisms associated with the development of renal functional changes after renal ablation.

Key Words: prostaglandins • cyclooxygenase • renal ablation • kidney failure • renal physiology

This article has been cited by other articles:

				C. Y.-C. Peng, D. Sankaran, M. R. Ogborn, and H. M. Aukema Dietary Soy Protein Selectively Reduces Renal Prostanoids and Cyclooxygenases in Polycystic Kidney Disease Experimental Biology and Medicine, July 1, 2009; 234(7): 737 - 743. [Abstract] [Full Text] [PDF]

				P. Michielsen, L. Heinemann, M. Mihatsch, P. Schnulle, H. Graf, and K.-M. Koch Non-phenacetin analgesics and analgesic nephropathy: Clinical assessment of high users from a case-control study [1]* Nephrol. Dial. Transplant., April 1, 2009; 24(4): 1253 - 1259. [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]

				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. Sankaran, N. Bankovic-Calic, M. R. Ogborn, G. Crow, and H. M. Aukema Selective COX-2 inhibition markedly slows disease progression and attenuates altered prostanoid production in Han:SPRD-cy rats with inherited kidney disease Am J Physiol Renal Physiol, September 1, 2007; 293(3): F821 - F830. [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]

				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]

				L. Warford-Woolgar, C. Y.-C. Peng, J. Shuhyta, A. Wakefield, D. Sankaran, M. Ogborn, and H. M. Aukema Selectivity of cyclooxygenase isoform activity and prostanoid production in normal and diseased Han:SPRD-cy rat kidneys Am J Physiol Renal Physiol, April 1, 2006; 290(4): F897 - F904. [Abstract] [Full Text] [PDF]

				R. C. Harris and M. D. Breyer Update on Cyclooxygenase-2 Inhibitors Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 236 - 245. [Abstract] [Full Text] [PDF]

				E. Vazquez, I. Coronel, R. Bautista, E. Romo, C. M. Villalon, M. C. Avila-Casado, V. Soto, and B. Escalante Angiotensin II-dependent induction of AT2 receptor expression after renal ablation Am J Physiol Renal Physiol, January 1, 2005; 288(1): F207 - F213. [Abstract] [Full Text] [PDF]

				M. C. LaPointe, M. Mendez, A. Leung, Z. Tao, and X.-P. Yang Inhibition of cyclooxygenase-2 improves cardiac function after myocardial infarction in the mouse Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1416 - H1424. [Abstract] [Full Text] [PDF]

				R. Nasrallah, A. Landry, S. Singh, M. Sklepowicz, and R. L. Hebert Increased expression of cyclooxygenase-1 and -2 in the diabetic rat renal medulla Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1068 - F1077. [Abstract] [Full Text]

				G. Gambaro Strategies to safely interfere with prostanoid activity while avoiding adverse renal effects: could COX-2 and COX-LOX dual inhibition be the answer? Nephrol. Dial. Transplant., July 1, 2002; 17(7): 1159 - 1162. [Full Text] [PDF]

				R. Bautista, A. Sanchez, J. Hernandez, A. Oyekan, and B. Escalante Angiotensin II Type AT2 Receptor mRNA Expression and Renal Vasodilatation Are Increased in Renal Failure Hypertension, September 1, 2001; 38(3): 669 - 673. [Abstract] [Full Text] [PDF]

				J. Hernandez, H. Astudillo, and B. Escalante Angiotensin II stimulates cyclooxygenase-2 mRNA expression in renal tissue from rats with kidney failure Am J Physiol Renal Physiol, April 1, 2002; 282(4): F592 - F598. [Abstract] [Full Text] [PDF]