Vol. 286, Issue 2, 704-708, August 1998

Indomethacin Inhibits the Natriuretic Effects of Neuropeptide Y in Anesthetized Rats¹

Angela Bischoff, Volker Limmroth and Martin C. Michel

Departments of Medicine (A.B., M.C.M.) and Neurology (V.L.), University of Essen, Essen, Germany

Neuropeptide Y (NPY) is a unique modulator of renal function that enhances urine flow and sodium excretion despite marked reductions in renal blood flow. We investigated whether the cyclooxygenase inhibitor indomethacin alters the renal NPY effects in anesthetized rats. Treatment with 5 mg/kg indomethacin i.p. lowered urinary prostaglandin excretion by 85%. Systemic infusion of NPY elevated mean arterial pressure by 15 mm Hg and renovascular resistance by 8.0 mm Hg/ml/min, whereas the related peptide YY_3-36 (PYY_3-36) did not. Nevertheless, both peptides enhanced urine flow rate by 250 and 100 µl/15 min, respectively, and sodium excretion by 15 µmol/15 min. Treatment with indomethacin did not affect NPY- and PYY_3-36-induced alterations of systemic and renovascular hemodynamics but completely abolished NPY- and PYY_3-36-induced diuresis and natriuresis. Endogenous creatinine clearance was not affected by any treatment. We conclude that cyclooxygenase-derived arachidonic acid metabolites are not involved in the systemic or renal hemodynamic effects of NPY and PYY_3-36 but mediate NPY- and PYY_3-36-induced diuresis and natriuresis.