title: Chronic treatment with angiotensin II type 1 receptor antagonist suppresses glomerular activator protein-1 activity in salt-sensitive hypertensive rats.
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.
authors.affiliation: Department of Medicine III, Okayama University Medical School, Okayama, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Otsuka
authors.forename: T
authors.initials: T
authors.lastname: Ogura
authors.forename: T
authors.initials: T
authors.lastname: Yamauchi
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Kataoka
authors.forename: J
authors.initials: J
authors.lastname: Kageyama
authors.forename: H
authors.initials: H
authors.lastname: Makino
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D017315:Cilazapril / Q000494:pharmacology; D003900:Desoxycorticosterone; D004586:Electrophoresis; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020303:Rats, Inbred Dahl; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D018808:Transcription Factor AP-1; D017315:Cilazapril; D003900:Desoxycorticosterone; C077793:candesartan cilexetil