Kameshima S, Sakamoto Y, Okada M, Yamawaki H
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori, Japan.
Acta Physiol (Oxf). 2016 Jun;217(2):120-9. doi: 10.1111/apha.12636. Epub 2015 Dec 24.
Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a relatively novel adipocytokine with protective effects on metabolic diseases including obesity and type II diabetes. We have previously demonstrated that vaspin exerts anti-inflammatory and antimigratory roles through antioxidative effects in vascular smooth muscle cells. As inflammatory responses and migration of smooth muscle in peripheral vascular wall are key mechanisms for the pathogenesis of hypertension, we hypothesized that vaspin could prevent the development of hypertension in in vivo hypertensive animal model.
Vaspin (1 μg kg(-1) day(-1) ) was administered intraperitoneally to 5-week-old male spontaneously hypertensive rats (SHR) for 4 weeks. Superior mesenteric artery was isolated and used for measurement of isometric contraction and histological analysis.
Long-term vaspin treatment significantly prevented an elevation of systolic blood pressure (SBP) at 8 weeks of age. Vaspin had no effect on reactivity of isolated mesenteric artery from SHR. In contrast, vaspin significantly inhibited mesenteric arterial wall hypertrophy in SHR. Moreover, vaspin significantly inhibited an increase of tumour necrosis factor-α expression and a production of reactive oxygen species in isolated mesenteric artery from SHR.
This study for the first time demonstrates that vaspin prevents the increase of SBP in SHR through inhibiting peripheral vascular hypertrophy possibly via antioxidative and anti-inflammatory mechanisms.
内脏脂肪组织衍生的丝氨酸蛋白酶抑制剂（内脏脂肪素）是一种相对较新的脂肪细胞因子，对包括肥胖症和II型糖尿病在内的代谢性疾病具有保护作用。我们之前已经证明，内脏脂肪素通过对血管平滑肌细胞的抗氧化作用发挥抗炎和抗迁移作用。由于外周血管壁平滑肌的炎症反应和迁移是高血压发病机制的关键机制，我们推测内脏脂肪素可以在体内高血压动物模型中预防高血压的发展。
将内脏脂肪素（1μg·kg⁻¹·天⁻¹）腹腔注射给5周龄雄性自发性高血压大鼠（SHR），持续4周。分离肠系膜上动脉，用于测量等长收缩和组织学分析。
长期内脏脂肪素治疗显著预防了8周龄时收缩压（SBP）的升高。内脏脂肪素对SHR分离的肠系膜动脉的反应性没有影响。相反，内脏脂肪素显著抑制了SHR肠系膜动脉壁肥厚。此外，内脏脂肪素显著抑制了SHR分离的肠系膜动脉中肿瘤坏死因子-α表达的增加和活性氧的产生。
本研究首次证明，内脏脂肪素可能通过抗氧化和抗炎机制抑制外周血管肥厚，从而预防SHR中SBP的升高。
