Historical text by DatBTrue, written between 2008 and 2016 and reproduced verbatim. It records what was argued then; it is not dosing guidance and not medical advice. Read the disclaimer.
The growth hormone secretagogues (GHS) are a family of synthetic compounds originally selected for their potent and specific effects on GH release. Nonetheless, it has been reported by us and other researchers that the GHS have also many extraendocrine actions, including those on energy metabolism and cardiovascular function. Ghrelin, the endogenous GHS, specifically binds to the GHS-R1a, a receptor that has been proposed to mediate the biological activities of endogenous and synthetic GHS.
The activation of the GHS-R1a is not enough to explain the results that we have previously reported on the ability of hexarelin, a synthetic full agonist of the GHS-R1a, to protect the rat heart from the damage induced by the ischemia-reperfusion procedure. In fact, the GHS-R1a is not expressed in the myocardium, and ghrelin is much less effective than hexarelin in protecting the heart from ischemia-reperfusion damage.
Moreover, it has also been demonstrated that in the cardiovascular system hexarelin and other GHS can also bind to the CD36, a scavenger receptor.
Interestingly, a large similitude exists between the cardioprotective effects of hexarelin and those of some angiotensin-converting enzyme (ACE)-inhibitors. For this reason, we have decided to ascertain whether hexarelin, ghrelin and other synthetic GHS can modify the catalytic activity of serum and tissue ACE in rats and humans.
Briefly, 10 ul of serum or tissue homogenate were incubated in presence of hippuryl-histidyl-leucine, a substrate of ACE that is cleaved to histidyl-leucine. The cleavage of the substrate was quantified by measuring the fluorescence at 365/495 nm (excitation/emission) in presence of orthophthaldialdehyde. Enalapril was chosen as reference ACE-inhibitor.
Hexarelin (1 to 100 uM) dose-dependently blunted ACE activity up to about 50% in rat and human plasma and rat lung, heart and kidney. Enalapril (0.1 to 5 uM) dose-dependently inhibited ACE activity in serum and tissues up to 85%. Ghrelin (1 to 100 uM) did not significantly modify serum and tissue ACE activity at all the concentrations tested, whereas other synthetic GHS-R1a ligands demonstrated a dose-dependent inhibition of ACE activity ranging from 10 to 85%.
We conclude that the protective actions of certain GHS on the cardiovascular system might be mediated, at least in part, by the capability of these compounds to modulate the ACE activity in the general circulation and locally in tissues. Source: Characterization of a Novel Extraendocrine Action of the Growth Hormone Secretagogues: Inhibition of Angiotensin-Converting Enzyme (ACE) Activity, A Torsello, M Ravelli, E Bresciani, I Bulgarelli, L Tamiazzo, S Caporali, V Locatelli,
Dept of Experimental Med, Univ of Milano-Bicocca, Monza, Italy; Interdepartmental Ctr for Bioinformatics Proteomics, Univ of Milano-Bicocca, Monza, Italy