PMID:12093889

Citation	Qi, Z, Hao, CM, Langenbach, RI, Breyer, RM, Redha, R, Morrow, JD and Breyer, MD (2002) Opposite effects of cyclooxygenase-1 and -2 activity on the pressor response to angiotensin II. J. Clin. Invest. 110:61-9
Abstract	Therapeutic use of cyclooxygenase-inhibiting (COX-inhibiting) nonsteroidal antiinflammatory drugs (NSAIDs) is often complicated by renal side effects including hypertension and edema. The present studies were undertaken to elucidate the roles of COX1 and COX2 in regulating blood pressure and renal function. COX2 inhibitors or gene knockout dramatically augment the pressor effect of angiotensin II (Ang II). Unexpectedly, after a brief increase, the pressor effect of Ang II was abolished by COX1 deficiency (either inhibitor or knockout). Ang II infusion also reduced medullary blood flow in COX2-deficient but not in control or COX1-deficient animals, suggesting synthesis of COX2-dependent vasodilators in the renal medulla. Consistent with this, Ang II failed to stimulate renal medullary prostaglandin E(2) and prostaglandin I(2) production in COX2-deficient animals. Ang II infusion normally promotes natriuresis and diuresis, but COX2 deficiency blocked this effect. Thus, COX1 and COX2 exert opposite effects on systemic blood pressure and renal function. COX2 inhibitors reduce renal medullary blood flow, decrease urine flow, and enhance the pressor effect of Ang II. In contrast, the pressor effect of Ang II is blunted by COX1 inhibition. These results suggest that, rather than having similar cardiovascular effects, the activities of COX1 and COX2 are functionally antagonistic.
Links	PubMed PMC151026 Online version:10.1172/JCI14752
Keywords	Angiotensin II/pharmacology; Animals; Anti-Inflammatory Agents, Non-Steroidal/adverse effects; Blood Pressure/drug effects; Blood Pressure/physiology; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors/adverse effects; Diuresis/physiology; Female; Humans; Isoenzymes/deficiency; Isoenzymes/genetics; Isoenzymes/physiology; Kidney/drug effects; Kidney/metabolism; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Natriuresis/physiology; Prostaglandin-Endoperoxide Synthases/deficiency; Prostaglandin-Endoperoxide Synthases/genetics; Prostaglandin-Endoperoxide Synthases/physiology; Prostaglandins/biosynthesis; Renal Circulation/drug effects
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