[Role of the renin-angiotensin system in cardiovascular and renal diseases].
Accumulating evidence indicate that various growth-related genes, growth factors and extracellular matrix components play a central role in the pathogenesis of cardiovascular and renal diseases by regulating cellular phenotype, growth and migration or promoting tissue fibrosis. Treatment of hypertensive rats with an angiotensin II type 1-receptor (AT1-receptor) antagonist normalizes cardiac phenotypic modulation and the increased fibrosis-related gene expressions in hypertrophied heart, leading to the improvement of cardiac dysfunction. The AT1-receptor antagonist can inhibit protooncogenes (c-fos, c-jun and Egr-1) and fibronectin gene expressions in rat balloon-injured artery, which is associated with the inhibition of neointima formation. Furthermore, the AT1-receptor antagonist prevents either the phenotypic modulation of glomerular mesangial cells or the increase in transforming growth factor-beta 1 expression in nephrosclerosis. Thus, the AT1-receptor antagonist in vivo potently inhibits the expression of growth-related gene and extracellular matrix and inhibits cellular phenotypic modulation. The AT1-receptor is responsible for the pathogenesis and development of cardiovascular and renal diseases.
Kim
S
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Department of Pharmacology, Osaka City University Medical School, Japan.
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000473:pathology; D005353:Fibronectins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D019808:Losartan; D011519:Proto-Oncogenes; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D005353:Fibronectins; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D019808:Losartan; C077793:candesartan cilexetil