Angiotensin II augments medullary hypoxia and predisposes to acute renal failure

European Journal of Clinical Investigation
M BrezisS Rosen

Abstract

The effects of angiotensin II (AII) upon medullary hypoxic injury and kidney function were investigated in vitro and in vivo. Synthetic AII added to perfusate of isolated rat kidneys reduced perfusion flow from 48 +/- 2 ml min-1 (+/- SE) to 19 +/- 1 (P less than 0.001) without altering glomerular filtration rate (GFR), raising filtration fraction from 1% to 3% (P less than 0.001). AII-extended hypoxic injury to medullary thick ascending limbs (mTAL) from 66 +/- 4% of tubules to 79 +/- 3 (P less than 0.05) in correlation with filtration fraction (r = 0.8, P less than 0.001). Addition of indomethacin (10(-4) mol l-1) further extended medullary hypoxic damage to 89 +/- 2% of mTAL (P less than 0.001). Uninephrectomized rats kept in metabolic cages were given AII by continuous infusion (0.1-0.8 microgram min-1) and indomethacin (10 mg kg-1 day-1) for 24 h. Creatinine clearance declined from 1.3 +/- 0.1 ml min-1 to 0.6 +/- 0.06 (P less than 0.001). Morphological examination revealed either selective necrosis of mTAL (in 12 +/- 4% of tubules) or luminal collapse (in 63 +/- 8%). Both necrosis and collapse correlated inversely with creatinine clearance and with each other (r = -0.5, P less than 0.001), the latter correlation suggesting ...Continue Reading

References

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Citations

Nov 30, 2000·Anesthesiology Clinics of North America·M Hladunewich, M H Rosenthal
Jul 8, 2000·Kidney International·D P Basile
Mar 9, 1995·The New England Journal of Medicine·M Brezis, S Rosen
Nov 5, 1999·Investigative Radiology·S N HeymanM Brezis
Dec 20, 2007·Current Opinion in Nephrology and Hypertension·Prabhleen SinghRoland C Blantz
Nov 28, 2012·Clinical and Experimental Pharmacology & Physiology·Peter HansellFredrik Palm
Aug 13, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Fredrik Palm, Lina Nordquist
Aug 1, 1991·The Journal of Clinical Investigation·M BrezisS Rosen
Sep 1, 1994·The Journal of Clinical Investigation·Y AgmonM Brezis
Feb 19, 2002·Kidney International·Dick de Zeeuw
Oct 1, 1991·Kidney International·S N HeymanS Rosen
Apr 23, 1999·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·S Donnelly, B R Shah
Apr 1, 1997·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·A C Simóes-e-SilvaR A Santos
Apr 19, 2018·American Journal of Physiology. Renal Physiology·Sofia JönssonMichael Hultström
Jun 1, 1993·Hypertension·P ErnsbergerJ G Douglas
Nov 9, 2007·Clinical Journal of the American Society of Nephrology : CJASN·Steven D Weisbord, Paul M Palevsky
Mar 16, 2001·American Journal of Physiology. Renal Physiology·D H KangR J Johnson
Aug 10, 2017·Cellular and Molecular Life Sciences : CMLS·Ovidiu C BaltatuJose Cipolla-Neto
Mar 26, 2003·Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions·Christopher S R Baker

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