Published Online
on June 26, 2006

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

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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

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