Differentiation of cyclooxygenase 1-and 2-derived prostanoids in mouse kidney and aorta

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. PGE(2) is the most abundant prostanoid in both renal cortex and medulla in normal C57BL/6J mice, followed by PGI(2), PGF(2 alpha) and thromboxane A(2). In contrast PGI(2) was most abundant in aorta followed by thromboxane A(2), PGE(2), and PGF(2 alpha). PGD(2) was undetectable in control kidney or aorta. At baseline, inhibition of COX 1 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 PGE(2) and PGI(2) in renal cortex and medulla. Anciotensin II also significantly increased renal PGF(2 alpha) in cortex, but not in medulla, through both COX1- and COX2-dependent mechanisms. These studies demonstrate that although COXI primarily contributes to basal prostanoid production in the kidney and aorta, angiotensin 11 increases renal vasodilator prostanoids predominately via COX2 activity. These effects may contribute to the specific effect of COX2 inhibitors to increase blood pressure.