Infusion of angiotensin-(1-7) reduced disease-induced increases in proteinuria by 75% and glomerular matrix accumulation by 48% in rats with experimental glomerulonephritis.
Does angiotensin-(1-7) infusion reduce glomerulosclerosis in rats with experimental glomerulonephritis?
In a rat model of experimental glomerulonephritis, continuous infusion of angiotensin-(1-7) significantly reduced proteinuria and markers of glomerulosclerosis, suggesting therapeutic potential for reversing renal fibrosis.
Absolute Event Rate: 26% vs 57%
p-value: p=<0.05
Recent identification of a counterregulatory axis of the renin-angiotensin system, called angiotensin-converting enzyme 2-angiotensin-(1-7) ANG-(1-7)-Mas receptor, may offer new targets for the treatment of renal fibrosis. We hypothesized that therapy with ANG-(1-7) would improve glomerulosclerosis through counteracting ANG II in experimental glomerulonephritis. Disease was induced in rats with the monoclonal anti-Thy-1 antibody, OX-7. Based on a three-dose pilot study, 576 microg x kg(-1) x day(-1) ANG-(1-7) was continuously infused from day 1 using osmotic pumps. Measures of glomerulosclerosis include semiquantitative scoring of matrix proteins stained for periodic acid Schiff, collagen I, and fibronectin EDA+ (FN). ANG-(1-7) treatment reduced disease-induced increases in proteinuria by 75%, glomerular periodic acid Schiff staining by 48%, collagen I by 24%, and FN by 25%. The dramatic increases in transforming growth factor-beta1, plasminogen activator inhibitor-1, FN, and collagen I mRNAs seen in disease control animals compared with normal rats were all significantly reduced by ANG-(1-7) administration (P < 0.05). These observations support our hypothesis that ANG-(1-7) has therapeutic potential for reversing glomerulosclerosis. Several results suggest ANG-(1-7) acts by counteracting ANG II effects: 1) renin expression in ANG-(1-7)-treated rats was dramatically increased as it is with ANG II blockade therapy; and 2) in vitro data indicate that ANG II-induced increases in mesangial cell proliferation and plasminogen activator inhibitor-1 overexpression are inhibited by ANG-(1-7) via its binding to a specific receptor known as Mas.
Zhang et al. (Thu,) conducted a other in Experimental glomerulonephritis (n=30). Angiotensin-(1-7) vs. Untreated disease control was evaluated on Urinary protein excretion (mg/24 h) (p=<0.05). Infusion of angiotensin-(1-7) reduced disease-induced increases in proteinuria by 75% and glomerular matrix accumulation by 48% in rats with experimental glomerulonephritis.