Effects of chronic inhibition of ACE and AT1 receptors on glomerular injury in Dahl salt-sensitive rats

Fumio Otsuka, Takayoshi Yamauchi, Hideo Kataoka, Yukari Mimura, Toshio Ogura, Hirofumi Marino

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

To elucidate the contribution of the renin-angiontensin system (RAS) to glomerular injury in salt-sensitive hypertension, we investigated the chronic effects of the angiotensin I-converting enzyme inhibitor cilazapril and the angiotensin II type 1-receptor antagonist (AT(1a)) TCV-116 in Dahl-Iwai rats. Dahl salt-sensitive (S) rats receiving 8% salt diet for 6 wk were simultaneously treated with cilazapril (n = 6), TCV-116 (n = 6), or saline (n = 14). The 8% salt diet markedly increased systolic blood pressure (SBP), urinary protein, and N-acetyl-β-glucosaminidase (NAG) excretion compared with 0.3% salt-treated S (n = 6) or salt-resistant (n = 6) rats. Although neither cilazapril nor TCV-116 reduced the elevated SBP, TCV-116 significantly lowered urinary protein and NAG excretion. Histologically, 8% salt treatment in S rats induced progressive sclerotic and proliferative glomerular changes, which were ameliorated by both drugs. TCV-116 increased the glomerular diameter. Immunofluorescence demonstrated the increased level of type III collagen in the mesangium of 8% salt-treated S rats, which was completely reversed by TCV-116. Competitive RT-PCR of mRNA extracted from the glomeruli revealed that 8% salt treatment significantly increased the levels of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor B-chain and that TCV-116 significantly reduced the levels of PCNA and transforming growth factor-β1 (TGF-β1). Thus, although the chronic RAS- inhibition in salt-sensitive hypertension exerted a histologically renoprotective effect by both ways without lowering blood pressure, the RAS inhibition due to AT(1a) had more beneficial advantages of reducing proteinuria and attenuating the levels of glomerular TGF-β1 and extracellular matrix.

Original languageEnglish
Pages (from-to)R1797-R1806
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume274
Issue number6 43-6
Publication statusPublished - Jul 14 1998

Keywords

  • Glomerulosclerosis
  • Platelet-derived growth factor B- chain
  • Proliferating cell nuclear antigen
  • Transforming growth factor- β1
  • Type III collagen

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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