title: Contribution of angiotensin II to late renal injury after acute ischemia.
abstract: Rats recovering from acute renal ischemia exhibit tubule loss and interstitial fibrosis followed by development of proteinuria and glomerular sclerosis. The current study assessed the contribution of angiotensin II (AngII) to these processes. The contribution of AngII to early tubule loss and interstitial fibrosis was assessed in rats studied for 35 d after right nephrectomy and transient occlusion of the left renal artery. One group of rats received no treatment, while a second group received losartan beginning at 2 d following ischemia. Studies at 35 d showed that losartan did not improve GFR (2.04 +/- 0.30 ml/min treated, 2.16 +/- 0.21 ml/min untreated), reduce the fraction of glomeruli that were no longer connected to normal tubule segments (42 +/- 9% treated, 42 +/- 13% untreated), or limit expansion of the interstitial volume fraction (25 +/- 3% treated, 25 +/- 4% untreated). The contribution of AngII to progressive glomerular injury following initial recovery from ischemia was assessed in similarly prepared rats studied for 140 d. One group of rats received no treatment, while a second group received enalapril beginning at 35 d following ischemia. Enalapril markedly reduced proteinuria (78 +/- 17 mg/d treated, 229 +/- 52 mg/d untreated) and the prevalence of segmental glomerular sclerosis (14 +/- 9% treated, 45 +/- 10% untreated). Untreated rats developed sclerotic lesions in glomeruli not connected to normal tubules, as well as in glomeruli connected to normal tubules. Enalapril prevented injury in both classes of glomeruli. These results indicate that AngII does not contribute to interstitial fibrosis during recovery from ischemic injury. Reduction of AngII activity, can, however, prevent secondary glomerular injury in kidneys initially damaged by ischemia.
authors.affiliation: Department of Medicine, VA Palo Alto Health Care System and Stanford University, Palo Alto, California.
authors.forename: Maria Enrica
authors.initials: ME
authors.lastname: Pagtalunan
authors.affiliation: Department of Pathology, University of California, San Francisco, California.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Olson
authors.affiliation: Department of Medicine, VA Palo Alto Health Care System and Stanford University, Palo Alto, California.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Meyer
mesh_terms: D000208:Acute Disease; D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D018450:Disease Progression; D004656:Enalapril / Q000494:pharmacology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D004656:Enalapril; D019808:Losartan