Chronic treatment with angiotensin II type 1 receptor antagonist suppresses glomerular activator protein-1 activity in salt-sensitive hypertensive rats

Fumio Otsuka, Toshio Ogura, Takayoshi Yamauchi, Minoru Sato, Hideo Kataoka, Jingo Kageyama, Hirofumi Makino

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We examined the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor antagonist (AT1a) on the action of protooncogene c-fos in salt-sensitive hypertensive rats. Seven-week old Dahl salt-sensitive rats fed a high (8%)-salt diet were treated with ACEI, cilazapril (10 mg/kg) or AT1a, TCV-116 (1 mg/kg) every day for 6 weeks. The control animals were fed a low (0.3%)-salt diet. Systolic blood pressure gradually increased in high-salt-loaded rats and was higher than low-salt-treated rats throughout the study. However, both medications had no significant antihypertensive effect. After 6 weeks of therapy, glomerular mRNA and nuclear protein were extracted from the resected kidneys. Competitive reverse transcription-polymerase chain reaction showed a high level of glomerular c-fos mRNA in high-salt-loaded rats and that ACEI or AT1a treatment did not significantly change its level. Electrophoretic mobility shift assay demonstrated that treatment with AT1a significantly decreased the activator protein-1 (AP-1) binding activity in the glomerular nuclear extract compared to ACEI. Our findings suggest that, compared with ACEI treatment, long-term treatment with AT1a may contribute to attenuation of the glomerular injury in salt-sensitive hypertension by inhibiting AP-1 transcription activity independent of its antihypertensive effect.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalKidney and Blood Pressure Research
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 1 2000

Keywords

  • Activator protein-1
  • Dahl salt-sensitive rats
  • Glomerulus
  • Renin-angiotensin system
  • c-fos

ASJC Scopus subject areas

  • Nephrology
  • Cardiology and Cardiovascular Medicine

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