High-protein diets augment albuminuria in rats with Heymann nephritis by angiotensin II-dependent and -independent mechanisms

George Kaysen, Sarah Webster, Hamoudi Al-Bander, Hardin Jones, Florence N. Hutchison

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 presser 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 presser 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 V(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.

Original languageEnglish (US)
Pages (from-to)238-245
Number of pages8
JournalMineral and Electrolyte Metabolism
Volume24
Issue number4
DOIs
StatePublished - Jul 1998

Fingerprint

Membranous Glomerulonephritis
Albuminuria
Losartan
Dietary Proteins
Nutrition
Angiotensin II
Rats
Diet
Enalapril
Proteins
Angiotensin-Converting Enzyme Inhibitors
Angiotensin I
Angiotensin Receptor Antagonists
Blood pressure
Caseins
Hypotension
Albumins
Blood Pressure

Keywords

  • Angiotensin receptor binding
  • Enalapril
  • Kinins
  • Losartan
  • Nephrotic syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

High-protein diets augment albuminuria in rats with Heymann nephritis by angiotensin II-dependent and -independent mechanisms. / Kaysen, George; Webster, Sarah; Al-Bander, Hamoudi; Jones, Hardin; Hutchison, Florence N.

In: Mineral and Electrolyte Metabolism, Vol. 24, No. 4, 07.1998, p. 238-245.

Research output: Contribution to journalArticle

Kaysen, George ; Webster, Sarah ; Al-Bander, Hamoudi ; Jones, Hardin ; Hutchison, Florence N. / High-protein diets augment albuminuria in rats with Heymann nephritis by angiotensin II-dependent and -independent mechanisms. In: Mineral and Electrolyte Metabolism. 1998 ; Vol. 24, No. 4. pp. 238-245.
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AB - 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 presser 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 presser 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 V(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.

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