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Acta Physiologica 2009; Volume 195, Supplement 669
The 88th Annual Meeting of The German Physiological Society
3/22/2009-3/25/2009
Giessen, Germany
COX-INHIBITION RESTORES RENAL ORGANIC ANION TRANSPORT AND POSITIVELY INFLUENCES RENAL OUTCOME IN A RAT MODEL OF ISCHEMIC ACUTE KIDNEY INJURY
Abstract number: O120
Sauvant1 C., Schneider2 R., Meusel2 M., Roder2 M., Renker2 S., Wanner2 C., Gekle3 M.
1Medizinische Fakultt,, Bay. Julius-Maximilians Universitt Wrzburg, Physiologisches Institut, Wrzburg
2Klinik fr Innere Medizin I, Bay. Julius-Maximilians Universitt Wrzburg, Nephrologische Abt., Wrzburg
3Medizinische Fakultt, Universitt Halle-Wittenberg, Julius-Bernstein-Institut fr Physiologie, Halle/Saale
We have previously shown that expression of renal organic anion transporters OAT1 and OAT3 is diminished by prostaglandin E2 (PGE2) (Sauvant et al. JASN 2006). In addition, we obtained evidence that both transporters are down regulated after renal ischemia (Schneider et al. AJP-renal 2007). As it is well known that PGE2 levels are increased after renal ischemia and PGE2 is generated by cyclooxygenases (COX), we investigated the effect of the COX-inhibitor indomethacin on expression of OAT1 and OAT3. Indomethacin was given at a low dose of 1mg/kg b.w. in a well established model of ischemic acute kidney injury (iAKI). iAKI was induced in rats by bilateral clamping of renal arteries for 45 min. Indomethacin was given intraperitoneally at the very end of the ischemic period, so that the drug could enter the kidneys as soon as reperfusion started. Sham treated animals served as controls. The amount of OAT1 and OAT3 was determined by real time PCR and western blot. PGE2 levels in blood and urine were measured by ELISA. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were analysed by measuring inulin- and PAH-clearance. All parameters were detected 24 h after ischemia. PAH net secretion, as well as PGE2-clearance and secretion were calculated, as PAH and PGE2 are well known substrates for renal organic anion transport. A substantial reduction of GFR, RPF, PAH net secretion and PGE2 clearance was observed 24 hours after ischemia, while sham treatment did not alter kidney function. Indomethacin did not influence kidney function in sham operated animals. However, in clamped animals indomethacin re-stored the expression of OAT1 and OAT3, as well as PAH net secretion and PGE2-clearance. Additionally, indomethacin restored kidney function as measured by GFR (totally) and RPF (partly).
In conclusion our study indicates that low dose indomethacin prevents ischemia induced down regulation of OAT1 and OAT3 and moreover has a substantial protective effect on kidney function after iAKI.
This study was supported by the IZKF Würzburg. Grant IZKF 34(1).
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Acta Physiologica 2009; Volume 195, Supplement 669 :O120