Growth-hormone-releasing peptide 6 (GHRP6) prevents oxidant cytotoxicity and reduces myocardial necrosis in a model of acute myocardial infarction

Abstract

Therapies aimed at enhancing cardiomyocyte survival following myocardial injury are urgently required. As GHRP6 [GH (growth hormone)-releasing peptide 6] has been shown to stimulate GH secretion and has beneficial cardiovascular effects, the aim of the present study was to determine whether GHRP6 administration reduces myocardial infarct size following acute coronary occlusion in vivo. Female Cuban Creole pigs were anaesthetized, monitored and instrumented to ensure a complete sudden left circumflex artery occlusion for 1 h, followed by a 72 h reperfusion/survival period. Animals were screened clinically before surgery and assigned randomly to receive either GHRP6 (400 microg/kg of body weight) or normal saline. Hearts were processed, and the area at risk and the infarct size were determined. CK-MB (creatine kinase MB) and CRP (C-reactive protein) levels and pathological Q-wave-affected leads were analysed and compared. Evaluation of the myocardial effect of GHRP6 also included quantitative histopathology, local IGF-I (insulin-growth factor-I) expression and oxidative stress markers. GHRP6 treatment did not have any influence on mortality during surgery associated with rhythm and conductance disturbances during ischaemia. Infarct mass and thickness were reduced by 78% and 50% respectively, by GHRP6 compared with saline (P<0.01). More than 50% of the GHRP6-treated pigs did not exhibit pathogological Q waves in any of the ECG leads. Quantitative histopathology and CK-MB and CRP serum levels confirmed the reduction in GHRP6-mediated necrosis (all P<0.05). Levels of oxidative stress markers suggested that GHRP6 prevented myocardial injury via a decrease in reactive oxygen species and by the preservation of antioxidant defence systems (all P<0.05). Myocardial IGF-I transcription was not amplified by GHRP6 treatment compared with the increase induced by the ischaemic episode in relation to expression in intact hearts (P<0.01). In conclusion, GHRP6 exhibits antioxidant effects which may partially contribute to reduce myocardial ischaemic damage.

Beneficial Effects of Growth Hormone-Releasing Peptide on Myocardial Oxidative Stress and Left Ventricular Dysfunction in Dilated Cardiomyopathic Hamsters

“…Berlanga et al recently showed that GHRP-6 treatment attenuated the decrease in total SOD activity in a model of acute myocardial infarction. 30 On the other hand, in the present study GSHPx activity did not differ among all 4 groups at 12 weeks of age. Although our findings suggest that antioxidant capacity might be relatively preserved in untreated TO-2 hamsters at 12 weeks of age, further enhancement of total SOD activity might in part contribute to the antioxidative effects of GHRP-2 in TO-2 hamsters.…”

Therapeutic Effect of the Combined Use of Growth Hormone Releasing Peptide-6 and Epidermal Growth Factor in an Axonopathy Model

“…Both are distinguished by their ability to turn multiple cell lineages into more tolerant before a broad spectrum of lethal insults (Berlanga et al 1998(Berlanga et al , 2002(Berlanga et al , 2007Caballero et al 2001;Cibrian et al 2006). EGF and GHRP-6 exhibit different biological properties which aim to hit the same pathophysiological targets, favoring at the end, neuronal and glial cells survival.…”

Role of Ghrelin in regulation of growth hormone secretion by Ghrelin-Pituitary-GH axis linkage

“…Previous administration of GHSs such as hexarelin or GHRP-6 leads, 2 h later, to a near complete blockade of GHRH-mediated GH secretion, a finding called heterologous desensitization. [22] Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl compounds that are believed to stimulate the release of GH by a direct effect on the pituitary somatotroph and by stimulation of growth hormone-releasing hormone (GHRH) release and/or via functional antagonism of somatostatin (SRIH) tone. [24] They also binds and activate hypothalamic GHS-R. Maier's study shows that cholinergic blockade with ATR suppresses ghrelin plasma concentrations and modulation of the cholinergic system with ATR, but not PD, influences the ability of different ghrelin dosages to induce GH release.…”