title: High-protein diets augment albuminuria in rats with Heymann nephritis by angiotensin II-dependent and -independent mechanisms.
abstract: Urinary albumin excretion (U(alb)V) increases following dietary protein augmentation (DPA) in nephrotic humans and rats. Angiotensin-converting enzyme inhibitors (ACEI) blunt, but do not entirely prevent, increased U(alb)V 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 U(alb)V. 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 U(alb)V 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. U(alb)V 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 U(alb)V 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 U(alb)V. We then increased dietary NaCl from 0.2% to 2% (HS) to determine whether En or Los would modulate U(alb)V after DPA when Ang-II activity was suppressed. En reduced the DPA-mediated increase in U(alb)V regardless of dietary NaCl, while Los was effective only in when dietary NaCl was reduced (0.2%), suggesting that under these conditions ACEI reduces U(alb)V by a mechanism that is independent of inhibition of Ang-II and that high protein diets augment U(alb)V by both Ang-II-independent and Ang-II-dependent mechanisms.
authors.affiliation: Department of Medicine, University of California Davis School of Medicine, 95616, USA. gakaysen@ucdavis.edu
authors.forename: G A
authors.initials: GA
authors.lastname: Kaysen
authors.forename: S
authors.initials: S
authors.lastname: Webster
authors.forename: H
authors.initials: H
authors.lastname: Al-Bander
authors.forename: H
authors.initials: H
authors.lastname: Jones
authors.forename: F N
authors.initials: FN
authors.lastname: Hutchison
mesh_terms: D000419:Albuminuria; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004044:Dietary Proteins / Q000008:administration & dosage*; D004656:Enalapril / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000652:urine*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004044:Dietary Proteins; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D004656:Enalapril; D019808:Losartan