title: A novel adipocytokine, omentin, inhibits monocrotaline-induced pulmonary arterial hypertension in rats.
abstract: Omentin is a novel adipocytokine mainly expressed in visceral rather than subcutaneous adipose tissue. Several epidemiological studies demonstrated the negative relationship between blood omentin level and occurrence of obesity, type 2 diabetes and hypertension. Increases of inflammatory responses, contractile reactivity and structural remodeling of vascular wall contribute to hypertension development. Our in vitro studies previously demonstrated that omentin inhibited 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 inhibit pulmonary arterial (PA) hypertension (PAH). PAH was induced by a single intraperitoneal injection of monocrotaline (MCT: 60 mg/kg) to rats. Omentin (18 μg/kg/day) was intraperitoneally treated for 14 days. Chronic omentin treatment inhibited MCT-induced increases in PA pressure. Omentin inhibited MCT-induced right ventricular hypertrophy as well as increase of lung to body weight ratio. Histologically, omentin inhibited MCT-induced PA hyperplasia. Further, omentin inhibited the impairment of both endothelium-dependent and -independent relaxations mediated by acetylcholine and sodium nitroprusside, respectively. In conclusion, we for the first time demonstrate that chronic omentin treatment inhibits MCT-induced PAH in rats via inhibiting vascular structural remodeling and abnormal contractile reactivity.
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Kazama
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan.
authors.forename: Muneyoshi
authors.initials: M
authors.lastname: Okada
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan. Electronic address: yamawaki@vmas.kitasato-u.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamawaki
mesh_terms: D000818:Animals; D016207:Cytokines / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000517:prevention & control*; D037102:Lectins / Q000502:physiology*; D008297:Male; D016686:Monocrotaline / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016207:Cytokines; D037102:Lectins; C000591992:omentin protein, rat; D016686:Monocrotaline
keywords: Adipokine; Pulmonary hypertension; Vascular biology; Vascular reactivity; Vascular remodeling