![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
M Gellai, M Jugus, T Fletcher, P Nambi, EH Ohlstein, JD Elliott and DP Brooks
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, USA.
The ability of the mixed endothelin (ETA/ETB) receptor antagonist (+/-)- SB 209670 to prevent and reverse ischemia-induced acute renal failure (ARF) was studied in rats with moderate and severe ARF. Uninephrectomized, chronically instrumented Sprague-Dawley rats were used. Moderate and severe ARF was induced by occlusion of the renal artery for 30 and 45 min, respectively. During the 24 hr after 30-min ischemia (moderate ARF), glomerular filtration rate (GFR) decreased by 95%, and fractional excretion of sodium increased from 0.6% to 10%. Infusion of (+/-)-SB 209670 at 10, 30 and 100 micrograms/kg.min for 30 min before, during and 60 min after renal ischemia had a moderate effect on renal function. Thus, with the highest dose, the ischemia- induced reduction in GFR was 70%. This dose, however, had no effect in rats when given before, during and after 45 min of renal ischemia (severe ARF). In contrast, when infused at 30 micrograms/kg.min for 3 hr on the day after ischemia, (+/-)-SB 209670 markedly increased survival rate (75%) in rats with severe ARF by significantly increasing tubular reabsorption of Na+, followed by a slow and gradual increase in GFR and reversal of the increase in plasma K+ concentration. Data from acute renal clearance studies in rats with moderate ARF showed that when infused 24 hr after ischemia, (+/-)-SB 209670 acutely reversed the impairment in sodium reabsorption without increasing GFR or renal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
This article has been cited by other articles:
|
|
 |
|
  Z. Miloradovic, M. Jerkic, D. Jovovic, N. Mihailovic-Stanojevic, J. G. Milanovic, G. Stosic, and J. Markovic-Lipkovski Bosentan and losartan ameliorate acute renal failure associated with mild but not strong NO blockade Nephrol. Dial. Transplant., September 1, 2007; 22(9): 2476 - 2484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jerkic, Z. Miloradovic, D. Jovovic, N. Mihailovic-Stanojevic, J. V. R. Elena, D. Nastic-Miric, G. Grujic-Adanja, A. Rodriguez-Barbero, J. Markovic-Lipkovski, S. B. Vojvodic, et al. Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure Nephrol. Dial. Transplant., January 1, 2004; 19(1): 83 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Yamashita, S. Kita, T. Iwamoto, M. Ogata, M. Takaoka, N. Tazawa, M. Nishikawa, K. Wakimoto, M. Shigekawa, I. Komuro, et al. Attenuation of Ischemia/Reperfusion-Induced Renal Injury in Mice Deficient in Na+/Ca2+ Exchanger J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 284 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Huang, C. Huang, D. Hestin, P. C. Dent, P. Barclay, M. Collis, and E. J. Johns The effect of endothelin antagonists on renal ischaemia-reperfusion injury and the development of acute renal failure in the rat Nephrol. Dial. Transplant., September 1, 2002; 17(9): 1578 - 1585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kato and A. Hishida Amelioration of post-ischaemic renal injury by contralateral uninephrectomy: a role of endothelin-1 Nephrol. Dial. Transplant., August 1, 2001; 16(8): 1570 - 1576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Itoh, M. Takaoka, A. Shibata, M. Ohkita, and Y. Matsumura Preventive Effect of Lactacystin, a Selective Proteasome Inhibitor, on Ischemic Acute Renal Failure in Rats J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 501 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yamashita, M. Itoh, T. Kuro, Y. Kobayashi, M. Ogata, M. Takaoka, and Y. Matsumura Pre- or Post-Ischemic Treatment with a Novel Na+/Ca2+ Exchange Inhibitor, KB-R7943, Shows Renal Protective Effects in Rats with Ischemic Acute Renal Failure J. Pharmacol. Exp. Ther., April 13, 2001; 296(2): 412 - 419. [Abstract] [Full Text]
|
|
|
|
 |
|
 N. LAMEIRE and R. VANHOLDER Pathophysiologic Features and Prevention of Human and Experimental Acute Tubular Necrosis J. Am. Soc. Nephrol., February 1, 2001; 12(90001): 20S - 32. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. Hu, Z. Chen, T. Fredrickson, M. Gellai, M. Jugus, L. Contino, N. Spurr, M. Sims, W. Halsey, S. Van Horn, et al. Identification of a novel kidney-specific gene downregulated in acute ischemic renal failure Am J Physiol Renal Physiol, September 1, 2000; 279(3): F426 - F439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Schiffrin Role of Endothelin-1 in Hypertension Hypertension, October 1, 1999; 34(4): 876 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Matsumura, N. Hashimoto, S. Taira, T. Kuro, R. Kitano, M. Ohkita, T. J. Opgenorth, and M. Takaoka Different Contributions of Endothelin-A and Endothelin-B Receptors in the Pathogenesis of Deoxycorticosterone Acetate–Salt–Induced Hypertension in Rats Hypertension, February 1, 1999; 33(2): 759 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kassab, J. Novak, T. Miller, K. Kirchner, and J. Granger Role of Endothelin in Mediating the Attenuated Renal Hemodynamics in Dahl Salt-Sensitive Hypertension Hypertension, September 1, 1997; 30(3): 682 - 686. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
