Obese patients have impaired vasodilator reactivity and increased endothelin (ET)-1-mediated vasoconstriction, two abnormalities contributing to vascular dysfunction. Obestatin, a product of the ghrelin gene, in addition to favorable effects on glucose and lipid metabolism, has shown nitric oxide (NO)-dependent vasodilator properties in experimental models. Given these premises, we compared the effects of exogenous obestatin on forearm flow in lean and obese subjects and assessed its influence on ET-1-dependent vasoconstrictor tone in obesity. In both lean and obese participants, infusion of escalating doses of obestatin resulted in a progressive increase in blood flow from baseline (both P<0.001); this vasodilation was predominantly mediated by enhanced NO activity, because L-NMMA markedly blunted the flow response to obestatin in both groups (both P<0.05 vs. saline). In obese subjects, antagonism of ETA receptors by BQ-123 increased forearm flow during saline (P<0.001), but did not induce additional vasodilation (P>0.05) during obestatin. Circulating obestatin levels were not different between lean and obese participants (P=0.41). Our findings indicate that obestatin causes NO-dependent vasodilation in the human circulation. This effect is preserved in obesity, where it is accompanied by reduced ET-1-mediated vasoconstriction. These latter observations make obestatin a promising target for vascular prevention in obesity and diabetes.
Schinzari, F., Veneziani, A., Mores, N., Barini, A., Di Daniele, N., Cardillo, C., et al. (2017). Vascular Effects of Obestatin in Lean and Obese Subjects. DIABETES, db161067 [10.2337/db16-1067].
|Tipologia:||Articolo su rivista|
|Citazione:||Schinzari, F., Veneziani, A., Mores, N., Barini, A., Di Daniele, N., Cardillo, C., et al. (2017). Vascular Effects of Obestatin in Lean and Obese Subjects. DIABETES, db161067 [10.2337/db16-1067].|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.2337/db16-1067|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||7-feb-2017|
|Titolo:||Vascular Effects of Obestatin in Lean and Obese Subjects|
|Autori:||Schinzari, F; Veneziani, A; Mores, N; Barini, A; Di Daniele, N; Cardillo, C; Tesauro, M|
|Appare nelle tipologie:||01 - Articolo su rivista|