Chronic Treatment with Angiotensin II Type 1 Receptor Antagonist Suppresses Glomerular Activator Protein–1 Activity in Salt–Sensitive Hypertensive Rats

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.