Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist

Abstract

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 + (K ATP ) 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 K ATP 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 K ATP channel agonist nicorandil. Addition of the K ATP channel blocker glibenclamide eliminated the beneficial effects of nicorandil against hypertrophy and on connexin43.In conclusion, the present study indicated that chronic use of K ATP channel agonists following cardiac hypertrophy can attenuate ventricular remodeling and upregulate the expression level and spatial distribution of Cx43.

Effects of heme oxygenase-1 upregulation on isoproterenol-induced myocardial infarction

“…Metias et al [17] reported similar changes in Cx-43 in ISO-induced MI. Also, Sun et al [53] concluded that the reduction and redistribution of myocardial Cx-43 might be mediated by ATP-sensitive potassium channels through preserving protein kinase C-dependent connexion-43 level after MI. Disruption of myocardial Cx-43 in the present study might be explained by enhanced oxidative stress in the heart tissues.…”

IK1 Channel Agonist Zacopride Alleviates Cardiac Hypertrophy and Failure via Alterations in Calcium Dyshomeostasis and Electrical Remodeling in Rats

“…In some cases of cardiac diseases, electrical remodeling, such as alterations in ion channels or Ca 2+ cycling, precedes the observed depression of mechanical performance, suggesting that amelioration of electrical remodeling might be an effective therapeutic strategy against HF (Houser and Margulies, 2003; Mueller et al, 2011). K ATP is reportedly involved in ventricular remodeling, and K ATP channel agonists exert beneficial effects on cardiac structural remodeling and dysfunction (Lee et al, 2008; Sun et al, 2015). I K1 and K ATP channels are both members of inward rectifier potassium (Kir) channel family and are respectively constituted by Kir2.x and Kir6.x subunits (Hibino et al, 2010).…”

Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels

“…Activation of K ATP channel has also been identified to attenuate the degree of myocardial hypertrophy by modulating the expression level and spatial distribution of Cx43 [42]. Our previous study investigated the effect of STV on sarc-and mitoK ATP channels and showed that STV could sensitize these K ATP channels in a ROS dependent manner [25].…”