Ghrelin protects the heart against ischemia-induced arrhythmias by preserving connexin-43 protein

Abstract

Vagal nerve stimulation has been postulated to confer an antifibrillatory effect. We studied whether ghrelin administration would exert an antiarrhythmic effect via modulation of autonomic nerve activity in rats after acute myocardial ischemia (MI). Male Sprague-Dawley rats were exposed to 30 min of ischemia following ligation of the left coronary artery. Animals were then randomized to receive either ghrelin (n = 26) or saline (n = 26) during the period of coronary ligation. Power spectral analysis of heart-rate variability revealed that the administration of ghrelin increased the high-frequency (HF) power and decreased the low-frequency (LF)/HF ratio. Ventricular tachyarrhythmias were less frequent in rats after MI who received ghrelin in comparison with rats that received saline. Immunoblotting and immunohistochemistry revealed that rats given saline alone during MI exhibited a marked reduction in phosphorylated connexin-43 within the left ventricle, whereas those that received ghrelin displayed only minor reductions in comparison with sham-operated rats. These effects of ghrelin were diminished by the coadministration of atropine or the blockade of vagal afferents. These data demonstrate that the beneficial effect of ghrelin might be mediated by modulation of cardiac autonomic nerve activity.

Dysregulation of Mfn2 and Drp-1 proteins in heart failure

“…Vagus nerve stimulation protects against ventricular arrhythmias during myocardial infarction (MI) by prevention of Cx-43 dephosphorylation. In support of this, the administration of ghrelin, which mimics vagal stimulation, mediated protection against ventricular arrhythmias in MI, through preservation of the phosphorylated Cx-43 levels (Soeki et al 2013). Further, fibroblast growth factor (FGF) induced protection against ischemic injury also comprises Cx-43 phosphorylation (Srisakuldee et al 2006).…”

Somatotropic and cardio-protective effects of ghrelin in experimental models of heart failure: A systematic review

“…[38] Modulation of sympathetic nervous system Ghrelin mediates cardioprotective effects by modulating cardiac autonomic nervous activity. [16] However; the precise mechanisms by which ghrelin regulates sympathetic activity are still unclear and needs further investigation. Peripheral ghrelin may act on GHS-R Ia at the cardiac vagal nerve ending, which goes to the nucleus of tractus solitarius and suppresses the renal SNA.…”

“…[9][10][11][12][13] Elevated levels of ghrelin have been found in patients with HF. [14] Various cardioprotective effects of ghrelin have been reported which includes reduction of peripheral vascular resistance, [15,16] improvement in myocardial contractility and antiinflammatory effects. [17] Clinical studies have reported that exogenous administration of ghrelin decreases muscle wasting, improves exercise capacity, improves left ventricular (LV) and endothelial function, increase myocardial contractility, dilate peripheral blood vessels, constricts the coronary arteries, reduces blood pressure, inhibits cardiomyocyte apoptosis, inhibit sympathetic nerve activity (SNA) and protects from HF induced by myocardial infarction.…”

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

“…These effects of ghrelin decreased with atropine pre-treatment or vagotomy. Ghrelin exerted antiarrhythmic effects in rats during acute MI via modulation of vagal activity by showing increased high-frequency (HF) component as an index of parasympathetic activity and decreased low-frequency (LF)/HF ratio as an index of sympathetic activity and restoration of phosphorylated connexin-43 protein levels [181].…”