Nitric oxide, anti-inflammatory drugs on renal prostaglandins and cyclooxygenase-2.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used as analgesics. They inhibit cyclooxygenases (COX), preventing the formation of prostaglandins, including prostacyclin and thromboxane. A serious side effect of COX-1 and COX-2 is renal damage. We report here that both a nonselective NSAID (aspirin, acetylsalicylic acid) and COX-2 selective NSAIDs (celecoxib and NS-398) diminished renal prostacyclin and thromboxane concentration in the renal medulla. NSAIDs failed to change COX-2 and iNOS (the inducible form of NO synthase) expression. A NO donor, B-NOD, preserved renal prostacyclin and thromboxane after administration of aspirin. PGI2 and COX-2 protein were mainly expressed in the renal medulla, whereas iNOS expression was greater in the cortex. B-NOD preserved renal prostacyclin levels after administration of NSAIDs.
Miyataka
Masaru
M
Huntington Medical Research Institutes, Department of Experimental Cardiology, Pasadena, Cal 91101, USA.
Rich
Kathryn A
KA
Ingram
Marylou
M
Yamamoto
Tadahiko
T
Bing
Richard J
RJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D011460:Prostaglandins F / Q000378:metabolism; D011720:Pyrazoles; D011817:Rabbits; D012459:Salicylates / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism
C413747:2-hydroxybenzoic acid 3-nitrooxymethylphenyl ester; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009566:Nitrates; D020030:Nitric Oxide Donors; D009578:Nitrobenzenes; D011453:Prostaglandins; D011460:Prostaglandins F; D011720:Pyrazoles; D012459:Salicylates; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D009569:Nitric Oxide; D013929:Thromboxane B2; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D001241:Aspirin; C100006:prostaglandin F1