(Hypertension. 2000;36:276.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Renal Changes Induced by a Cyclooxygenase-2 Inhibitor During Normal and Low Sodium Intake
From the Departamento de Fisiología (F.R., M.T.L., J.D.G., F.J.S.), Facultad de Medicina, Murcia, Spain; and the Unidad de Hematología y Oncología Clínica (J.R.), Centro Regional de Hemodonación, Murcia, Spain.
Correspondence to Dr F. Javier Salazar, Departamento de Fisiología, Facultad de Medicina, 30100 Murcia, Spain. E-mail salazar{at}fcu.um.es
Abstract—Cyclooxygenase-2 (COX-2) has been identified in renal tissues under normal conditions, with its expression enhanced during sodium restriction. To evaluate the role of COX-2–derived metabolites in the regulation of renal function, we infused a selective inhibitor (nimesulide) in anesthetized dogs with normal or low sodium intake. The renal effects elicited by nimesulide and a non–isozyme-specific inhibitor (meclofenamate) were compared during normal sodium intake. In ex vivo assays, meclofenamate, but not nimesulide, prevented the platelet aggregation elicited by arachidonic acid. During normal sodium intake, nimesulide infusion (n=6) had no effects on arterial pressure or renal hemodynamics but did reduce urinary sodium excretion, urine flow rate, and fractional lithium excretion. In contrast, nimesulide administration increased arterial pressure and decreased renal blood flow, urine flow rate, and fractional lithium excretion during low sodium intake (n=6). COX-2 inhibition reduced urinary prostaglandin E2 excretion in both groups but did not modify plasma renin activity in dogs with low (8.1±1.1 ng angiotensin I · mL-1 · h-1) or normal (1.8±0.4 ng angiotensin I · mL-1 · h-1) sodium intake. Meclofenamate infusion in dogs with normal sodium intake (n=8) induced a greater renal hemodynamic effect than nimesulide infusion. These results suggest that COX-2–derived metabolites (1) are involved in the regulation of sodium excretion in dogs with normal sodium intake, (2) play an important role in the regulation of renal hemodynamic and excretory function in dogs with low sodium intake, and (3) are not involved in the maintenance of the high renin levels during a long-term decrease in sodium intake.
Key Words: renal circulation • kidney • cyclooxygenase • sodium • renin • prostaglandins
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