Effects of nonsteroidal anti-inflammatory drugs upon intrarenal blood flow: selective medullary hypoperfusion.
Nonsteroidal anti-inflammatory drugs (NSAIDs) predispose to acute and chronic renal failure, possibly due to intrarenal hemodynamic effects. In anesthetized volume-expanded rats, total renal blood flow (RBF) was measured by an ultrasonic flowmeter placed around the left renal artery, superficial cortical blood flow (sCBF) by a flunt laser-Doppler probe placed over the kidney surface, mid-cortical (mCBF) and outer medullary blood flow (oMBF) by a needle laser-Doppler probe inserted into the renal parenchyma. Indomethacin (5 mg/kg i.v.) caused no significant change in RBF (n = 9) or mCBF (n = 6) and slightly increased sCBF (to 106 +/- 2% of baseline; n = 8, p < 0.05). By contrast, oMBF dropped significantly (to 55 +/- 4% of baseline; n = 8, p < 0.0001) within 30 min of indomethacin administration. Similarly, acetylsalicylate (50 mg/kg i.v.) slightly increased sCBF (to 110 +/- 3% of baseline; n = 5, p < 0.05) but caused a significant drop in oMBF (to 54 +/- 2% of baseline; n = 5, p < 0.0001). These results suggest that NSAIDs cause a profound and selective reduction in oMBF which may predispose to acute or chronic intrarenal damage by aggravating medullary hypoxia.
Agmon
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Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.
Brezis
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007679:Kidney Medulla / Q000098:blood supply*; D017078:Laser-Doppler Flowmetry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin; D007213:Indomethacin