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

Kidney Blood Press Res. 2000;23(1):35-41. doi: 10.1159/000025952.

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 (1mg/ 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.

MeSH terms

  • Angiotensin Receptor Antagonists*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Antihypertensive Agents / therapeutic use*
  • Benzimidazoles / therapeutic use*
  • Biphenyl Compounds / therapeutic use*
  • Blood Pressure / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Chronic Disease
  • Cilazapril / pharmacology
  • Desoxycorticosterone
  • Electrophoresis
  • Heart Rate / drug effects
  • Hypertension / chemically induced
  • Hypertension / metabolism*
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism*
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-fos / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Inbred Dahl
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetrazoles*
  • Transcription Factor AP-1 / antagonists & inhibitors*
  • Transcription Factor AP-1 / biosynthesis

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Benzimidazoles
  • Biphenyl Compounds
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Tetrazoles
  • Transcription Factor AP-1
  • Cilazapril
  • Desoxycorticosterone
  • candesartan cilexetil