Dietary salt intake modulates progression of antithymocyte serum nephritis through alteration of glomerular angiotensin II receptor expression

Am J Physiol Renal Physiol. 2004 Feb;286(2):F267-77. doi: 10.1152/ajprenal.00059.2003. Epub 2003 Oct 14.

Abstract

Dietary salt intake modulates the renin-angiotensin system (RAS); however, little is known about the effect of salt intake on the progression of glomerulonephritis. We investigated the glomerular expression of TGF-beta1 type I (TbetaRI) and II (TbetaRII) TGF-beta receptors and RAS components in rats with antithymocyte serum (ATS) nephritis on normal (NSI)-, low (LSI)-, and high-salt intake (HSI) and on HSI rats receiving candesartan cilexetil (CC) and LSI rats receiving PD-123319. Glomerular lesions were less severe in rats on LSI and aggravated in those on HSI compared with those on NSI. Intrarenal renin and glomerular ANG II levels were significantly higher in LSI and lower in HSI rats. In ATS nephritis, HSI increased glomerular TbetaRI, TbetaRII, and ANG II type 1 receptor (AT1R), and decreased glomerular ANG II type 2 receptor (AT2R), whereas LSI decreased glomerular TGF-beta1 and TbetaRI and increased glomerular AT2R. CC ameliorated glomerular lesions, reduced glomerular TGF-beta1 and TbetaRII, and increased glomerular AT2R. PD-123319 aggravated glomerular lesions and increased glomerular TGF-beta1 and TbetaRII. Our results suggest that dietary salt intake influences progression of ATS nephritis by modulating glomerular TGF-beta1 and TbetaR expression resulting, at least in part, from altered glomerular AT1R and AT2R expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism
  • Angiotensin II Type 2 Receptor Blockers
  • Animals
  • Blood Pressure
  • Body Weight
  • Female
  • Glomerulonephritis / metabolism*
  • Glomerulonephritis / pathology
  • Imidazoles / pharmacology
  • Kidney Glomerulus / metabolism*
  • Macrophages / pathology
  • Pyridines / pharmacology
  • Receptor, Angiotensin, Type 1 / metabolism*
  • Receptor, Angiotensin, Type 2 / metabolism*
  • Receptors, Transforming Growth Factor beta / metabolism
  • Renin / blood
  • Sheep
  • Sodium Chloride, Dietary / pharmacology*
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1

Substances

  • Angiotensin II Type 2 Receptor Blockers
  • Imidazoles
  • Pyridines
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, Transforming Growth Factor beta
  • Sodium Chloride, Dietary
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Angiotensin II
  • PD 123319
  • Renin