Preferential COX-2 Inhibitor, Meloxicam, Compromises Renal Perfusion in Euvolemic and Hypovolemic Rats

Abstract

Nonsteroidal anti-inflammatory drugs can impair renal perfusion through inhibition of cyclooxygenase (COX)-mediated prostaglandin synthesis. We investigated the influence of the preferential COX-2 inhibitor, meloxicam (MELO), on renal hemodynamics in eu- and hypovolemic rats compared to the nonselective COX inhibitor indomethacin (INDO). The hypovolemic state was obtained in rats by three daily injections of furosemide (2 mg/kg i.p.) followed by a sodium-deficient diet for 7 days. In euvolemic rats (n = 6) neither INDO (5 mg/kg i.v.) nor MELO (1 or 2 mg/kg i.v.) influenced mean arterial blood pressure (MAP) or impaired renal (RBF) and cortical blood flow (CBF). Medullary blood flow (MBF) decreased after INDO (18%; p < 0.05), and dose-dependently after MELO (1 mg, 10%; 2 mg, 18%; p < 0.05). In hypovolemic rats (n = 6) INDO and MELO had no effect on MAP. RBF and CBF were reduced after INDO (11 or 20%; p < 0.05), but showed no changes after MELO. INDO induced a decrease in MBF (22%; p < 0.05) which was less pronounced after MELO (12%; p < 0.05). In conclusion the preferential COX-2 inhibitor MELO compromized renal perfusion in the outer medulla both in eu- and hypovolemic animals.