title: Possible involvement of Rho-kinase in aldosterone-induced vascular smooth muscle cell remodeling.
abstract: There is increasing evidence supporting potential roles of aldosterone in the pathogenesis of vascular injury. The present study aimed to determine the involvement of Rho-kinase in aldosterone-induced vascular smooth muscle cell (VSMC) remodeling. In cultured rat VSMC, the effects of aldosterone on Rho-kinase activity, the reorganization of the cytoskeleton and cellular migration were examined. Aldosterone (1 nmol/L) significantly increased phosphorylation of myosin phosphate target subunit-1 (MYPT1), a marker of Rho-kinase activity, and the amount of GTP-Rho with a peak at 90 min in VSMC. Aldosterone also stimulated VSMC stress fiber formation and migration. These effects of aldosterone were markedly attenuated by pretreatment with eplerenone (10 micromol/L), a selective mineralocorticoid receptor antagonist, or Y27632 (10 micromol/L), a specific Rho-kinase inhibitor. These findings indicate that Rho-kinase is involved in the pathogenesis of aldosterone-induced VSMC remodeling.
authors.affiliation: Life Sciences Research Center, Kagawa University Medical School, Kagawa, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Miyata
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hitomi
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.forename: Guo-Xing
authors.initials: GX
authors.lastname: Zhang
authors.forename: Shoji
authors.initials: S
authors.lastname: Kimura
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Kiyomoto
authors.forename: Naohisa
authors.initials: N
authors.lastname: Hosomi
authors.forename: Shoji
authors.initials: S
authors.lastname: Kagami
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D000199:Actins / Q000737:chemistry; D000450:Aldosterone / Q000633:toxicity*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000473:pathology; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases / Q000502:physiology*
chemical_list: D000199:Actins; D000577:Amides; D000451:Mineralocorticoid Receptor Antagonists; D011725:Pyridines; C108830:Y 27632; D000450:Aldosterone; D054460:rho-Associated Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1