Treatment With a Growth Hormone Secretagogue in a Model of Developing Heart Failure

Abstract

The improved LV pump function that occurred with GHS treatment in this model of CHF was most likely a result of favorable effects on LV myocardial remodeling and contractile processes. On the basis of these results, further studies are warranted to determine the potential role of GH secretagogues in the treatment of CHF.

Beneficial effects of high doses of growth hormone in the introduction and optimization of medical treatment in decompensated congestive heart failure

“…Multiple mechanisms appear to be involved including: (1) GH reducing LV peak wall stress by increasing wall thickness and ventricular mass without inducing reactive fibrosis, stimulating smooth muscle cell proliferation, increasing the capillary density, normalizing SR Ca 2+ -ATPase activity, improving myocardial contractility or the response to an inotropic stimulus, and reducing oxygen consumption [17,18,[25][26][27][28][29]; (2) overcoming the acquired GH resistance characteristic of cachectic CHF patients [8,15,30]; (3) resolving endothelial dysfunction by restoring nitric oxide (NO) production, influencing the Ca 2+ concentration, or regulating Na + -K + -ATPase activity or structural changes in the vascular bed [16,31]; (4) reducing the rate of apoptosis in myocardial and skeletal muscle [32,33]; (5) reducing norepinephrine levels, thus, sympathetic activation [25,34]; (6) increasing diuresis and sodium excretion, probably by enhancing renal NO system activity [35]; (8) stimulating phosphorylation of the h 2 -adrenergic receptor [36]; (9) down-regulating fetal genes regarded as markers of CHF progression [37]; (10) reducing collagen volume fraction (%) [12]; (11) reducing circulating proinflammatory cytokines, soluble Fas/soluble Fas ligand, and soluble adhesion molecules [38,39]; and (12) improving endothelial dysfunction [40]. Then, the observed improvement in our patients could be explained by multiple actions of GH.…”

Growth hormone-releasing peptide can improve left ventricular dysfunction and attenuate dilation in dilated cardiomyopathic hamsters

“…In addition to its stimulatory effect on GH secretion, hexarelin, a hexapeptide member of the GHRP family, protected against postischemic dysfunction in perfused hearts isolated from senescent rats [17]. Furthermore, treatment with a GH secretagogue was beneficial in a model of developing heart failure [18]. It has remained unclear, however, whether the cardioprotective effects of GHRP are mediated, at least in part, by a mechanism independent of the GH-IGF-1 axis.…”

Ghrelin in the heart and growth hormone: which is chicken, which is egg?

“…GHS treatment provides beneficial effects on left ventricular structure and function in the experimental model of rapid pacing-induced heart failure in pig [5]. In this first study, benefits of GHS treatment are mostly imputed to a release of endogenous GH.…”

“…In this first study, benefits of GHS treatment are mostly imputed to a release of endogenous GH. However, the possibility that GHS have direct cardiovascular effects, independent of GH release, has been suggested because of different effects between GH supplementation and GHS treatment [5] and because GHSR(s) are present in the heart [6,7]. Binding properties of rat heart GHSR(s) have been characterized using hexarelin, a GHS compound with strong GH-releasing activity [6].…”