Vascular Effects of Obestatin in Lean and Obese Subjects.

Abstract

Obese patients have impaired vasodilator reactivity and increased endothelin 1 (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 NG-monomethyl-l-arginine 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.

• Authors: Francesca Schinzari, Augusto Veneziani, Nadia Mores, Angela Barini, Nicola Di Daniele, Carmine Cardillo, Manfredi Tesauro
• Journal: Diabetes (Diabetes) Vol. 66 Issue 5 Pg. 1214-1221 (05 2017) ISSN: 1939-327X [Electronic] United States
• PMID: 28174289 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 by the American Diabetes Association.

Chemical References

• Endothelin A Receptor Antagonists
• Endothelin-1
• Enzyme Inhibitors
• Ghrelin
• Peptides, Cyclic
• omega-N-Methylarginine
• Nitric Oxide
• cyclo(Trp-Asp-Pro-Val-Leu)

Topics

• Adult
• Case-Control Studies
• Endothelin A Receptor Antagonists (pharmacology)
• Endothelin-1
• Endothelium, Vascular (drug effects)
• Enzyme Inhibitors (pharmacology)
• Female
• Forearm (blood supply)
• Ghrelin (pharmacology)
• Humans
• Male
• Nitric Oxide (metabolism)
• Obesity, Abdominal
• Peptides, Cyclic (pharmacology)
• Regional Blood Flow (drug effects)
• Vasoconstriction (drug effects)
• Vasodilation (drug effects)
• omega-N-Methylarginine (pharmacology)