Effects of nonsteroidal anti-inflammatory drugs on prostacyclin and thromboxane in the kidney.
Dose-response curves were obtained relating the effects of increasing amounts of aspirin, a nonselective cyclooxygenase (COX) inhibitor, and celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, on the concentrations of prostacyclin and thromboxane in renal cortex and medulla of rabbits. The concentrations of the two agonists (aspirin and celecoxib) which elicit a half-maximal response on the prostanoid concentration (EC(50)) were compared. Additionally, controls for prostacyclin and thromboxane were related to values for the experimental groups. The EC(50) values for celecoxib were considerably lower than those for aspirin, indicating that celecoxib was more effective in suppressing prostanoid production. There were also significant differences between the majority of experimental groups and their respective controls, further evidence for the greater inhibitory activity of celecoxib on prostacyclin. Celecoxib lowered the ratio prostacyclin/thromboxane in the renal medulla; mercuric chloride further diminished the concentration of prostacyclin in the renal medulla. The results confirm that in the normal rabbit kidney, both nonselective and specific COX inhibitors interfere with renal prostanoid synthesis, but that a selective COX-2 inhibitor is more effective.
Lomnicka
Magdalena
M
Department of Experimental Cardiology, Huntington Medical Research Institutes, Pasadena, California 91101, USA.
Karouni
Katayoun
K
Sue
Michele
M
Wessel
Lauren A
LA
Bing
Richard J
RJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D000068579:Celecoxib; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D011464:Epoprostenol / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000494:pharmacology; D011720:Pyrazoles; D011817:Rabbits; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology; D013931:Thromboxanes / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D013449:Sulfonamides; D013931:Thromboxanes; D008627:Mercuric Chloride; D011464:Epoprostenol; D000068579:Celecoxib; D001241:Aspirin