Possible involvement of Rho-kinase in aldosterone-induced vascular smooth muscle cell remodeling.
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.
Miyata
Kayoko
K
Life Sciences Research Center, Kagawa University Medical School, Kagawa, Japan.
Hitomi
Hirofumi
H
Guo
Peng
P
Zhang
Guo-Xing
GX
Kimura
Shoji
S
Kiyomoto
Hideyasu
H
Hosomi
Naohisa
N
Kagami
Shoji
S
Kohno
Masakazu
M
Nishiyama
Akira
A
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*
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