Volume 60, Issue 6, Pages 2283-2289 (December 2001) S3226, a novel NHE3 inhibitor, attenuates ischemia-induced acute renal failure in rats  Dr Max Hropot, Hans-Paul Juretschke, Karl Heinz Langer, Jan-Robert Schwark  Kidney International  Volume 60, Issue 6, Pages 2283-2289 (December 2001) DOI: 10.1046/j.1523-1755.2001.00058.x Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 1 Effects of intravenous infusion of S3226 in acute renal failure (ARF) on plasma creatinine (A), blood urea nitrogen (BUN; B), sodium (C) and potassium (D). Renal arteries were occluded for 40 minutes. S3226 was infused for 30 minutes before ischemia (; N = 12) or after release of clamps (; N = 12) at a dose of 20 mg/kg. Control rats received saline in a volume of 6.25 mL/kg (; N = 12). Values are means ± SEM, *P < 0.05 vs. control group. Kidney International 2001 60, 2283-2289DOI: (10.1046/j.1523-1755.2001.00058.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 1 Effects of intravenous infusion of S3226 in acute renal failure (ARF) on plasma creatinine (A), blood urea nitrogen (BUN; B), sodium (C) and potassium (D). Renal arteries were occluded for 40 minutes. S3226 was infused for 30 minutes before ischemia (; N = 12) or after release of clamps (; N = 12) at a dose of 20 mg/kg. Control rats received saline in a volume of 6.25 mL/kg (; N = 12). Values are means ± SEM, *P < 0.05 vs. control group. Kidney International 2001 60, 2283-2289DOI: (10.1046/j.1523-1755.2001.00058.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 2 Effect of S3226 on renal intracellular pH of fasted uninephrectomized rats as monitored by in vivo 31P NMR spectroscopy. The drug was infused twice to maintain suitable blood levels as indicated in the labeled boxes at a dose of 20 mg/kg over 30 minutes. (A) S3226 did not affect pHi during normoxia (N = 4 each group). (B) S3226 was infused prior to and 5 minutes before ending of ischemia. In the S3226 group (N = 8 for each group) pHi was significantly reduced by 0.15 units (P < 0.05) during the 5-hour reperfusion period. Values are means ± SEM. Symbols are: (●) control, (□) drug. *P < 0.05 vs. control group. Kidney International 2001 60, 2283-2289DOI: (10.1046/j.1523-1755.2001.00058.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 3 Overview of the kidney cortex from a control (A) and a treated (B) rat. In panel A, tubular single or group necrosis (often extruded into the lumen), tubular dilation and diffusely distributed round cell infiltration in a broadened interstitium are visible, but these lesions are not observed in panel B. PAS staining, magnification ×160. Kidney International 2001 60, 2283-2289DOI: (10.1046/j.1523-1755.2001.00058.x) Copyright © 2001 International Society of Nephrology Terms and Conditions