EFFECT OF ANG-II RECEPTOR ANTAGONIST ON ALBUMINURIA AND RENAL-FUNCTION IN PASSIVE HEYMANN NEPHRITIS

Angio-tensin-converting enzyme inhibitors reduce albuminuria in nephrotic subjects, but the hormonal mechanism of this effect is not known. To determine whether specific inhibition of angio-tensin (ANG) II activity would decrease albuminuria as occurs after converting enzyme inhibition, rats with passive Heymann nephritis received enalapril or the ANG II receptor antagonist losartan (6 mg.kg-1.day-1) for 4 days. Enalapril reduced both albuminuria (from 583 +/- 53 to 286 +/- 55 mg/day, P < 0.001) and the fractional clearance of albumin (FC(Alb)) each day after starting treatment but did not affect glomerular filtration rate (GFR). Losartan reduced albuminuria significantly only after 4 days of treatment, but this value was not different from controls. GFR significantly increased with losartan (from 1.24 +/-0.09 to 1.73 +/- 0.21 ml/min, P < 0.05) so that FC(Alb) was reduced (from 0.0134 +/- 0.0027 to 0.0080 +/- 0.0018, P < 0.05). Blood pressure decreased only in the enalapril group. Although plasma renin activity increased and the pressor response to ANG I was inhibited by both enalapril and losartan, suggesting effective peripheral blockade of ANG II activity, a third group of nephrotic rats was treated with losartan (18 mg.kg-1.day-1) to ensure that adequate ANG II blockade was achieved. Blood pressure decreased 10 mmHg, GFR increased from 1.35 +/- 0.14 to 1.79 +/- 0.12 ml/min (P < 0.01), but albuminuria and FC(Alb) did not change. Urinary total kallikrein excretion was increased only in nephrotic rats treated with enalapril. Although both enalapril and losartan reduce ANG II activity, only the converting enzyme inhibitor reduces albuminuria. These differences in effect on blood pressure, albuminuria, GFR, and urinary kallikrein excretion suggest that the beneficial effect of enalapril on albuminuria may not be due to inhibition of ANG II activity.