HIGH-PROTEIN DIETS AUGMENT ALBUMINURIA IN RATS WITH HEYMANN NEPHRITISBY ANGIOTENSIN-II-DEPENDENT AND ANGIOTENSIN-II-INDEPENDENT MECHANISMS

Urinary albumin excretion (UalbV) increases following dietary protein augmentation (DPA) in nephrotic humans and rats, Angiotensin-convertin g enzyme inhibitors (ACEI) blunt, but do not entirely prevent, increas ed UalbV at doses that reduce blood pressure and entirely block the pr esser effect of exogenously administered angiotensin I (Ang-I), sugges ting 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 Heyma nn 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 fashio n in treated and untreated rats, even though Los caused hypotension an d prevented the presser effect of infused Ang-II, Only on day 6 after DPA did UalbV decrease, We then measured the effect of duration of pre treatment with Los on Ang-II binding to isolated glomeruli, Maximal in hibition 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, pretrea tment with either Les or En for 6 days entirely prevented any increase in UalbV We then increased dietary NaCl from 0.2% to 2% (HS) to deter mine whether En or Los would modulate UalbV after DPA when Ang-II acti vity was suppressed, En reduced the DPA-mediated increase in UalbV reg ardless of dietary NaCl, while Los was effective only in when dietary NaCl was reduced (0.2%), suggesting that under these conditions ACEI r educes UalbV by a mechanism that is independent of inhibition of Ang-I I and that high protein diets augment UalbV by both Ang-II-independent and Ang-II-dependent mechanisms.