title: Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist.
abstract: Cardiac hypertrophy is a compensatory mechanism that occurs in conjunction with cardiovascular diseases. Although hypertrophy of the myocardium provides certain benefits during the early stages of cardiovascular disease, prolonged hypertrophy is potentially harmful to the heart and can result in arrhythmia and heart failure. The aim of this study was to investigate whether an ATP‑sensitive K+ (KATP) channel agonist was capable of reducing isoproterenol (Iso)‑induced cardiac hypertrophy and modulating myocardial connexin43 (Cx43) expression. Fifty male Sprague Dawley rats were randomly assigned to five groups: Normal, vehicle, nicorandil, glibenclamide and nicorandil plus glibenclamide. Rats in the four treatment groups received Iso injection for seven days, followed by administration with saline, nicorandil, glibenclamide or a combination of nicorandil and glibenclamide, respectively, for four weeks. Cardiac hypertrophy was then evaluated by measuring body weight, heart weight and left‑ventricular weight, and plasma B‑type natriuretic peptide levels were evaluated by ELISA. Immunocytochemistry and a reverse transcription‑polymerase chain reaction were performed to detect the spatial distribution and gene expression of myocardial Cx43, respectively. The KATP channel agonist nicorandil markedly attenuated the degree of myocardial hypertrophy induced by Iso as compared with the vehicle group. Myocardial Cx43 expression was significantly decreased and redistributed following cardiac hypertrophy. The decrease and redistribution of Cx43 was reduced following treatment with the KATP channel agonist nicorandil. Addition of the KATP channel blocker glibenclamide eliminated the beneficial effects of nicorandil against hypertrophy and on connexin43. In conclusion, the present study indicated that chronic use of KATP channel agonists following cardiac hypertrophy can attenuate ventricular remodeling and upregulate the expression level and spatial distribution of Cx43.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Sun
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Chun-Miao
authors.initials: CM
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Emergency, The First People's Hospital of Hefei, Hefei, Anhui 230051, P.R. China.
authors.forename: Yu-Yu
authors.initials: YY
authors.lastname: Hao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Yang-Jing
authors.initials: YJ
authors.lastname: Xie
authors.affiliation: Department of Cardiology, The First People's Hospital of Hefei, Hefei, Anhui 230051, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Wang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018031:Connexin 43 / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007545:Isoproterenol / Q000009:adverse effects*; D054086:KATP Channels / Q000819:agonists*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D020108:Nicorandil / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
chemical_list: D018031:Connexin 43; D054086:KATP Channels; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D020108:Nicorandil; D007545:Isoproterenol