Effect of angiotensin II blockade on renal injury in mineralocorticoid-salt hypertension

Kidney function and structure were compared in control rats (group 1) and i n 3 groups of rats made hypertensive by administration of aldosterone and s aline for 8 weeks (groups 2, 3, and 4). Group 2 rats received only aldoster one and saline, while group 3 also received losartan and group 4 also recei ved enalapril. Rats in all groups were subjected to uninephrectomy before b eginning the experiment. Hypertension and proteinuria in rats given aldoste rone and saline were not affected by losartan or enalapril (8-week values f or blood pressure in mm Hg: 135+/-3 group 1, 193+/-4 group 2, 189+/-4 group 3, 189+/-5 group 3; P<0.05 groups 2, 3, and 4 versus 1; 8-week values for proteinuria in mg/d: 44+/-8 group 1, 278+/-34 group 2, 267+/-37 group 3, 28 9+/-36 group 4; P<0.05 groups 2, 3, and 4 versus 1), Vascular, glomerular, and tubulointerstitial injury accompanied hypertension and proteinuria at 8 weeks. Losartan and enalapril did not prevent vascular injury, which was c haracterized by thickening of arterial and arteriolar walls and by fibrinoi d necrosis and thrombotic microangiopathy. Likewise, losartan and enalapril did not reduce the prevalence of glomerular segmental sclerosis (1+/-1% gr oup i, 10+/-2% group 2, 11+/-2% group 3, 13+/-2% group 4; P<0.05 groups 2, 3, and 4 venus 1) or limit tubulointerstitial injury as reflected by the vo lume fraction of the cortical interstitium (15+/-1% group 1, 20+/-1% group 2, 21+/-1% group 3, 21+/-1% group 4; P<0.05 groups 2, 3, and 4 versus 1). T hese findings suggest that local angiotensin LI activity does not contribut e to the development of renal injury in mineralocorticoid-salt hypertension .