Published Online
on June 26, 2006

A more recent version of this article appeared on August 1, 2006

This Article Full Text (PDF) All Versions of this Article: 48/2/323    most recent 01.HYP.0000231934.67549.b7v1 Alert me when this article is cited Alert me if a correction is posted 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 Qi, Z. Articles by Breyer, M. D. Search for Related Content PubMed PubMed Citation Articles by Qi, Z. Articles by Breyer, M. D. Related Collections Lipids

Submitted on March 16, 2006
Revised on April 5, 2006

Differentiation of Cyclooxygenase 1- and 2-Derived Prostanoids in Mouse Kidney and Aorta

Zhonghua Qi^*; Hui Cai; Jason D. Morrow; and Matthew D. Breyer

From the Division of Nephrology (Z.Q., M.D.B.), Department of Medicine, and the Departments of Internal Medicine (H.C.), Pharmacology (J.D.M.), and Molecular Physiology and Biophysics (M.D.B.), Vanderbilt University, Nashville, Tenn; and the Veterans Administration Medical Center (M.D.B.), Nashville, Tenn.

^* To whom correspondence should be addressed. E-mail: zhonghua.qi{at}vanderbilt.edu.

Abstract--Accumulating evidence indicates cyclooxygenase (COX) 1 and COX2 differentially regulate cardiovascular and renal function. We have demonstrated previously in mice that COX2 inhibition enhances angiotensin II-induced hypertension, and COX1 inhibition attenuates the pressor effect of angiotensin II. To further elucidate the mechanism underlying the functional difference of COX1 versus COX2 inhibition, the present studies examined the prostaglandin (PG) profiles derived in COX1- or COX2-inhibited mouse kidney and aorta using gas chromatographic/mass spectrometric assays. PGE₂ is the most abundant prostanoid in both renal cortex and medulla in normal C57BL/6J mice, followed by PGI₂, PGF₂ and thromboxane A₂. In contrast PGI₂ was most abundant in aorta followed by thromboxane A₂, PGE₂, and PGF₂. PGD₂ was undetectable in control kidney or aorta. At baseline, inhibition of COX1 decreased total prostaglandins in renal cortex, medulla, and aorta, whereas COX2 inhibition decreased total prostaglandins only in renal medulla. Angiotensin II infusion significantly increased COX2-dependent/COX1-independent PGE₂ and PGI₂ in renal cortex and medulla. Angiotensin II also significantly increased renal PGF₂ in cortex, but not in medulla, through both COX1- and COX2-dependent mechanisms. These studies demonstrate that although COX1 primarily contributes to basal prostanoid production in the kidney and aorta, angiotensin II increases renal vasodilator prostanoids predominately via COX2 activity. These effects may contribute to the specific effect of COX2 inhibitors to increase blood pressure.

Key words: prostaglandins • cyclooxygenase • angiotensin II • kidney • mice

This article has been cited by other articles:

				J. Azzarello, K.-M. Fung, and H.-K. Lin Tissue Distribution of Human AKR1C3 and Rat Homolog in the Adult Genitourinary System J. Histochem. Cytochem., September 1, 2008; 56(9): 853 - 861. [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]

				H. R. Ansari, A. Nadeem, S. L. Tilley, and S. J. Mustafa Involvement of COX-1 in A3 adenosine receptor-mediated contraction through endothelium in mice aorta Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3448 - H3455. [Abstract] [Full Text] [PDF]

				M.-E. Gendron and E. Thorin A change in the redox environment and thromboxane A2 production precede endothelial dysfunction in mice Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2508 - H2515. [Abstract] [Full Text] [PDF]

				O. B. Vagnes, B. M. Iversen, and W. J. Arendshorst Short-term ANG II produces renal vasoconstriction independent of TP receptor activation and TxA2/isoprostane production Am J Physiol Renal Physiol, September 1, 2007; 293(3): F860 - F867. [Abstract] [Full Text] [PDF]

				Y. Alvarez, J. V. Perez-Giron, R. Hernanz, A. M. Briones, A. Garcia-Redondo, A. Beltran, M. J. Alonso, and M. Salaices Losartan Reduces the Increased Participation of Cyclooxygenase-2-Derived Products in Vascular Responses of Hypertensive Rats J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 381 - 388. [Abstract] [Full Text] [PDF]