Vasodilatory Effect of Ghrelin, an Endogenous Peptide From the Stomach

Abstract

Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, which is identified as an endogenous ligand for GH secretagogues receptor. Although both ghrelin and its specific receptor are expressed in blood vessels, the cardiovascular effects of ghrelin remain unknown. To clarify whether ghrelin has a vasodilatory effect in humans, the response of forearm blood flow (FBF) to intra-arterial infusion of ghrelin was examined in eight healthy volunteers using a plethysmograph. In addition, hormonal responses to ghrelin were studied. Ghrelin increased FBF in a dose-dependent manner. Pretreatment with NG-monomethyl-l-arginine (l-NMMA), a nitric oxide synthase inhibitor, did not inhibit the FBF response to ghrelin, although l-NMMA significantly inhibited GH release. Serum insulin-like growth factor-I (IGF-I) level was not altered by ghrelin administration. Plasma cyclic guanosine 3', 5'-monophosphate level, a second messenger of nitric oxide, was also not altered. These results suggest that ghrelin has vasodilatory effects possibly through GH/IGF-I/nitric oxide-independent mechanisms.

Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln14-ghrelin

“…The involvement of prostacyclin was also confirmed by direct detection of increased amounts of 6-keto-PGF 1a released after des-octanoyl ghrelin application. On the other hand, ghrelin effects are neither accompanied by alterations of plasma cyclic guanosine 3,5-monophosphate level nor inhibited by pretreatment with nitric oxide synthase inhibitors, suggesting NO-independent mechanism of action (Okumura et al, 2002). It has been reported that ghrelin may modulate sympathetic nerve activity (Matsumura et al, 2002).…”

“…In vivo studies have demonstrated that ghrelin exerts cardiac actions also in humans (Okumura et al, 2002;Nagaya and Kangawa, 2003). Ghrelin administration induces hemodynamic effects in man either in normal subjects or in patients with dilated cardiomyopathy, reducing cardiac afterload and increasing cardiac output, without an increase in heart rate (Nagaya and Kangawa, 2003).…”

“…In fact, it has been reported that ghrelin increases food intake, adiposity and causes a positive energy balance, as well as modulates glucose metabolism and cell growth in non-tumoural and neoplastic tissues . In addition, as a result of studies conducted in vitro and in vivo, it has been already reported that ghrelin not only exerts cardiovascular effects in humans Okumura et al, 2002;Nagaya and Kangawa, 2003), but it has also been demonstrated that ghrelin does not share all cardiac activities exerted by synthetic GHS (Torsello et al, 2003). Interestingly, besides GHS type 1a receptor mRNA expression (Nagaya and Kangawa, 2003) and specific binding sites labelled by [ 125 I]His 9 -ghrelin (Katugampola et al, 2001), animal and human myocardium possess also GHS receptors that are specific for peptidyl GHS and which do not recognise ghrelin or the non-peptidyl GHS, MK-0677 (Bodart et al, 1999;Papotti et al, 2000).…”

Endothelial dysfunction and arterial abnormalities in childhood obesity

“…[97][98][99] There is evidence that all of these obesity-related peptides alter vascular tone or function. [100][101][102][103] Additionally, resistin, adiponectin and ghrelin all influence the expression of CAMs on vascular endothelial cells. [104][105][106] Childhood obesity and atherosclerosis MR Skilton and DS Celermajer Finally, the physical stresses that accompany increases in body mass may contribute to cardiovascular disease.…”

Obestatin regulates cardiovascular function and promotes cardioprotection through the nitric oxide pathway

“…These peptides have been shown to modulate cardiac inotropism 5, 6, 7, 8 and vascular tone 9, 10, 11, 12, 13, 14, and to reduce cell death and contractile dysfunction in hearts subjected to ischaemia/reperfusion (I/R) 15, 16, 17.…”