Preferential COX-2 inhibitor, meloxicam, compromises renal perfusion in euvolemic and hypovolemic rats.
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.
Birck
R
R
5th Department of Medicine, University Hospital Mannheim, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany. rbirck@rumms.uni-mannheim.de
Krzossok
S
S
Knoll
T
T
Braun
C
C
van Der Woude
F J
FJ
Rohmeiss
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D020896:Hypovolemia / Q000503:physiopathology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D007679:Kidney Medulla / Q000098:blood supply; D017078:Laser-Doppler Flowmetry; D008297:Male; D000077239:Meloxicam; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013843:Thiazines; D013844:Thiazoles; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000077239:Meloxicam