Urinary albumin excretion (UalbV) increases following dietary protein augmentation (DPA) in nephrotic humans and rats. Angiotensin-converting enzyme inhibitors (ACEI) blunt, but do not entirely prevent, increased UalbV at doses that reduce blood pressure and entirely block the pressor effect of exogenously administered angiotensin I (Ang-I), suggesting that angiotensin II (Ang-II) might not mediate the effect of DPA on UalbV. We determined the effect of losartan (Los), a specific Ang-II receptor antagonist, and compared its effect to that of enalapril (En), an ACEI, on DPA-induced increase in UalbV in rats with passive Heymann nephritis (HN). When Los was administered to HN rats for 48 h prior to DPA from 8.5 to 40% casein. UalbV increased in an identical fashion in treated and untreated rats, even though Los caused hypotension and prevented the pressor effect of infused Ang-II. Only on day 6 after DPA did UalbV decrease. We then measured the effect of duration of pretreatment with Los on Ang-II binding to isolated glomeruli. Maximal inhibition of Ang-II binding required treatment with Los for 6 days. We then pretreated HN rats with either En or Los for 6 days prior to DPA. In contrast to administration of Los for 2 days prior to DPA, pretreatment with either Los or En for 6 days entirely prevented any increase in UalbV. We then increased dietary NaCl from 0.2% to 2% (HS) to determine whether En or Los would modulate UalbV after DPA when Ang-II activity was suppressed. En reduced the DPA-mediated increase in UalbV regardless of dietary NaCl, while Los was effective only in when dietary NaCl was reduced (0.2%), suggesting that under these conditions ACEI reduces UalbV by a mechanism that is independent of inhibition of Ang-II and that high protein diets augment UalbV by both Ang-II-independent and Ang-II-dependent mechanisms.