CARDIOVASCULAR NEWS

Ghrelin Improves Endothelial Function in Patients With Metabolic Syndrome
 

Metabolic syndrome accelerates the atherosclerotic process, the earliest event of which is endothelial dysfunction. Ghrelin, a gastric peptide with cardiovascular actions, has been shown to inhibit proatherogenic changes in experimental models. The effect of ghrelin administration on endothelial function in patients with metabolic syndrome was investigated.
Endothelium-dependent and independent vasodilator responses to intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside (SNP), respectively, were assessed by strain-gauge plethysmography before and after local administration of human ghrelin (200 µg/min). During saline, the vasodilator response to acetylcholine was significantly blunted (P = 0.008) in patients with metabolic syndrome (n = 12, 5 female) compared with controls (n = 12, 7 female), whereas the vasodilator response to SNP was not different between groups (P = 0.68). In patients with metabolic syndrome, basal plasma ghrelin was significantly lower than in controls
(P = 0.02). In these patients, ghrelin infusion markedly increased intravascular concentrations of the peptide (P < 0.001) and resulted in a potentiation of the vasodilator response to acetylcholine (P = 0.001 versus saline) but not to SNP (P = 0.22). This effect was likely related to enhanced nitric oxide bioavailability because, in a group of patients with metabolic syndrome
(n = 6, 2 female), ghrelin had no effect on the vasodilator response to acetylcholine (P = 0.78 versus saline) after nitric oxide inhibition by NG-monomethyl-L-arginine.
The findings in this study indicate that Ghrelin reverses endothelial dysfunction in patients with metabolic syndrome by increasing nitric oxide bioactivity, thereby suggesting that decreased circulating levels of the peptide, such as those found in metabolic syndrome patients, might play a role in the pathobiology of atherosclerosis.
Circulation. 2005;112:2986-2992