Premium
Beneficial Effects of ATP‐sensitive potassium channels on Ventricular Remodeling in Infarcted Rats: Role of 70‐kDa S6 kinase
Author(s) -
Lee TsungMing,
Lin MeiShu,
Tsai ChangHer,
Chang NenChung
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1200-a
Subject(s) - pinacidil , nicorandil , glibenclamide , atp sensitive potassium channel , medicine , potassium channel , endocrinology , ventricular remodeling , potassium channel opener , chemistry , myocardial infarction , pharmacology , diabetes mellitus
Myocardial ATP‐sensitive potassium (K ATP ) channels have been implicated in left ventricular (LV) remodeling by inhibition of 70‐kDa S6 (p70S6) kinase. We assessed whether K ATP channel agonists exert beneficial effect on the structural, functional, and molecular features of LV remodeling in infarcted rats. After ligation of the anterior descending artery, male Wistar rats were randomized to either vehicle, agonists of K ATP channels nicorandil and pinacidil, an antagonist of K ATP channels glibenclamide, or a combination of nicorandil and glibenclamide or pinacidil and glibenclamide for 4 weeks. Significant LV hypertrophy was detected by increased myocyte size isolated by enzymatic dissociation after infarction. Rats in the nicorandil‐ and pinacidil‐treated groups significantly attenuated LV hypertrophy, as compared with the vehicle‐treated group. LV shortening fraction was significantly higher in the nicorandil‐ or pinacidil‐treated groups compared with the vehicle‐treated group. Increased expression of p70S6 kinase mRNA was confirmed by RT‐PCR, consistent with the results of immunohistochemistry and Western blot for the phosphorylation of p70S6 kinase. The beneficial effects of nicorandil and pinacidil were abolished by administering glibenclamide. Thus, activation of K ATP channels can attenuate LV remodeling through a S6 kinase‐dependent pathway after infarction.