Indomethacin inhibits the natriuretic effects of neuropeptide Y in anesthetized rats.
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 approximately 85%. Systemic infusion of NPY elevated mean arterial pressure by approximately 15 mm Hg and renovascular resistance by approximately 8.0 mm Hg/ml/min, whereas the related peptide YY3-36 (PYY3-36) did not. Nevertheless, both peptides enhanced urine flow rate by approximately 250 and approximately 100 microl/15 min, respectively, and sodium excretion by approximately 15 micromol/15 min. Treatment with indomethacin did not affect NPY- and PYY3-36-induced alterations of systemic and renovascular hemodynamics but completely abolished NPY- and PYY3-36-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 PYY3-36 but mediate NPY- and PYY3-36-induced diuresis and natriuresis.
Bischoff
A
A
Department of Medicine, University of Essen, Essen, Germany.
Limmroth
V
V
Michel
M C
MC
D000758:Anesthesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015232:Dinoprostone / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009478:Neuropeptide Y; D015232:Dinoprostone; D007213:Indomethacin