Effects of angiotensins on cellular hypertrophy and c-fos expression in cultured arterial smooth muscle cells.
An increase in cell size and protein content was observed when quiescent arterial smooth muscle cells in culture were incubated with either angiotensin II or III. These effects were inhibited by the specific angiotensin type-1 receptor antagonist losartan (DuP753) but not by CGP42112A. In parallel, a transient and dose-dependent induction of c-fos was demonstrated not only with angiotensins II and III but also with angiotensin I. Both angiotensins II and III exerted their maximal effect at 1 microM, while angiotensin I needed a tenfold-higher concentration to exert an identical effect. As for hypertrophy, losartan also inhibits angiotensin-induced c-fos expression, suggesting that this gene may be involved into the hypertrophic process. Angiotensin-I-mediated c-fos induction is partially inhibited by the angiotensin-converting enzyme inhibitors captopril and trandolaprilate; given that an angiotensin-converting enzyme activity was detected in these smooth muscle cell cultures, these results suggest that angiotensin-I-induced c-fos expression is mediated in part via angiotensin-I conversion to angiotensin II, but also by other unidentified pathway(s). Angiotensin I could essentially induce smooth muscle cell hypertrophy by indirect mechanisms, while angiotensins II and III act directly on smooth muscle cells.
Millet
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D
Unité 8 de Cardiologie de l'Institut National de la Santé et de la Recherche Médicale, Pessac, France.
Desgranges
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C
Campan
M
M
Gadeau
A P
AP
Costerousse
O
O
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000809:Angiotensins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D019808:Losartan; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D012313:RNA / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D001713:Biphenyl Compounds; D007093:Imidazoles; D007211:Indoles; D009842:Oligopeptides; D016760:Proto-Oncogene Proteins c-fos; D013777:Tetrazoles; C060894:CGP 42112A; C052035:trandolapril; D012313:RNA; D004247:DNA; D002216:Captopril; D019808:Losartan