Abstract 582: A Novel Adipocytokine, Omentin, Prevents Monocrotaline-induced Pulmonary Arterial Hypertension In Rats

Abstract

Background: Omentin is a novel adipocytokine mainly expressed in visceral rather than subcutaneous adipose tissue. Several epidemiological reports demonstrate the negative relationship between serum omentin level and occurrence of obesity, type 2 diabetes and hypertension. Increase of inflammatory responses, contractile reactivity and structural remodeling of vascular wall contributes to hypertension development. Our in vitro and ex vivo studies previously demonstrated that omentin prevented those hypertension-related pathological processes. In addition, our in vivo study demonstrated that intravenously injected omentin acutely inhibited agonists-induced increases of blood pressure in rats. However, the chronic effects of omentin on hypertension development are not determined. In the present study, we tested the hypothesis that chronic omentin treatment may prevent monocrotaline (MCT)-induced pulmonary arterial (PA) hypertension (PAH). Methods and Results: MCT-induced PAH was induced by a single intraperitoneal injection of MCT (60 mg/kg) to rats. Omentin (18 μg/kg/day) was intraperitoneally treated for 14 days. Chronic omentin inhibited MCT-induced increases in PA pressure (n=8-10, p<0.05). Omentin inhibited MCT-induced increases in right ventricular hypertrophy (n=6-8, p<0.01) as well as lung to body weight ratio (n=8, p<0.01). Histologically, omentin inhibited MCT-induced PA hyperplasia (n=8, p<0.01). Omentin prevented the impairment of both endothelium-dependent and-independent relaxations mediated by acetylcholine and sodium nitroprusside, respectively (n=7-13, p<0.01). Conclusion: We for the first time demonstrate that chronic omentin treatment inhibits MCT-induced PAH in rats via preventing endothelial dysfunction and/or vascular structural remodeling.