Abstract | OBJECTIVES: We investigated the effects of an angiotensin II type 1 (AT1)-receptor antagonist on experimental cardiac hypertrophy, vascular thickening and nephrosclerosis, in order to determine the involvement of this receptor in the development of cardiovascular and renal damage. DESIGN: Accumulating evidence indicates that various growth-related genes, growth factors and extracellular matrix components play a central part in the pathogenesis and development of cardiovascular and renal diseases, either by regulating cell growth and migration or by promoting tissue fibrosis. MATERIALS AND METHODS:
Stroke-prone spontaneously hypertensive rats were given candesartan cilexetil, a specific non- peptide AT1-receptor antagonist, for 10 weeks, and cardiac phenotypic and fibrosis-related gene expression and aortic and mesenteric arterial gene expressions were determined. Balloon-injured carotid arteries and deoxycorticosterone acetate ( DOCA)- salt hypertensive rats were also similarly examined. RESULTS: Treatment of hypertensive rats with an AT1-receptor antagonist led to the regression of cardiac hypertrophy, suppression of cardiac phenotypic changes to a fetal phenotype and an increase in fibrosis-related gene expression in the hypertrophied heart. Balloon injury-induced neointima formation in the rat carotid artery was prevented by the AT1-receptor antagonist, which was associated with the inhibition of the induction of proto-oncogenes such as c-fos, c-jun and Egr-1 and of increased fibronectin gene expression. Furthermore, the AT1-receptor antagonist prevented either the phenotypic modulation of glomerular cells or an increase in transforming growth factor-beta 1 expression in an experimental model of nephrosclerosis. CONCLUSIONS: AT1-receptor antagonists in vivo potently inhibit the expression of the growth-related and extracellular matrix genes, as well as cellular phenotypic modulation. These molecular effects of the AT1-receptor antagonist may contribute to their protective effects on cardiovascular and renal diseases.
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Authors | S Kim, H Iwao |
Journal | Journal of hypertension. Supplement : official journal of the International Society of Hypertension
(J Hypertens Suppl)
Vol. 15
Issue 6
Pg. S3-7
(Dec 1997)
ISSN: 0952-1178 [Print] England |
PMID | 9493120
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
- Angiotensin Receptor Antagonists
- Antihypertensive Agents
- Benzimidazoles
- Biphenyl Compounds
- Fibronectins
- Proto-Oncogene Proteins
- RNA, Messenger
- Receptor, Angiotensin, Type 1
- Receptor, Angiotensin, Type 2
- Receptors, Angiotensin
- Tetrazoles
- Angiotensin II
- candesartan cilexetil
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Topics |
- Angiotensin II
(physiology)
- Angiotensin Receptor Antagonists
- Animals
- Antihypertensive Agents
(pharmacology)
- Benzimidazoles
(pharmacology)
- Biphenyl Compounds
(pharmacology)
- Cardiomegaly
(metabolism, physiopathology, prevention & control)
- Fibronectins
(genetics, metabolism)
- Gene Expression
(drug effects)
- Humans
- Hypertension
(drug therapy, metabolism, physiopathology)
- Nephrosclerosis
(metabolism, physiopathology, prevention & control)
- Proto-Oncogene Proteins
(genetics, metabolism)
- RNA, Messenger
(metabolism)
- Rats
- Rats, Inbred SHR
- Rats, Inbred WKY
- Receptor, Angiotensin, Type 1
- Receptor, Angiotensin, Type 2
- Receptors, Angiotensin
(physiology)
- Tetrazoles
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