Contribution of angiotensin II to late renal injury after acute ischemia

Rats recovering from acute renal ischemia exhibit tubule loss and interstit ial fibrosis followed by development of proteinuria and glomerular sclerosi s. The current study assessed the contribution of angiotensin II (AngII) to these processes. The contribution of AngII to early tubule loss and inters titial fibrosis was assessed in rats studied for 35 d after right nephrecto my and transient occlusion of the left renal artery. One group of rats rece ived no treatment, while a second group received losartan beginning at 2 d following ischemia. Studies at 35 d showed that losartan did not improve GF R (2.04 +/- 0.30 ml/min treated, 2.16 +/- 0.21 ml/min untreated), reduce th e fraction of glomeruli that were no longer connected to normal tubule segm ents (42 +/- 9% treated, 42 +/- 13% untreated), or limit expansion of the i nterstitial volume fraction (25 +/- 3% treated, 25 +/- 4% untreated). The c ontribution of AngII to progressive glomerular injury following initial rec overy 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 pre valence of segmental glomerular sclerosis (14 +/- 9% treated, 45 +/- 10% un treated). Untreated rats developed sclerotic lesions in glomeruli not conne cted to normal tubules, as well as in glomeruli connected to normal tubules , Enalapril prevented injury in both classes of glomeruli. These results in dicate that AngII does not contribute to interstitial fibrosis during recov ery from ischemic injury. Reduction of AngII activity, can, however, preven t secondary glomerular injury in kidneys initially damaged by ischemia.