Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada 034-8628, Aomori, Japan.
School of Veterinary Medicine, Kitasato University Veterinary Teaching Hospital, Higashi 23 Bancho 35-1, Towada 034-8628, Aomori, Japan.
Int J Mol Sci. 2023 Feb 14;24(4):3835. doi: 10.3390/ijms24043835.
Hypertension is one of the major risk factors for cardiovascular diseases and is caused by various abnormalities including the contractility of blood vessels. Spontaneously hypertensive rats (SHR), whose systemic blood pressure increases with aging, are a frequently used animal model for investigating essential hypertension and related complications in humans due to the damage of several organs. Human omentin-1 is an adipocytokine consisting of 313 amino acids. Serum omentin-1 levels decreased in hypertensive patients compared with normotensive controls. Furthermore, omentin-1 knockout mice showed elevated blood pressure and impaired endothelial vasodilation. Taken together, we hypothesized that adipocytokine, human omentin-1 may improve the hypertension and its complications including heart and renal failure in the aged SHR (65-68-weeks-old). SHR were subcutaneously administered with human omentin-1 (18 μg/kg/day, 2 weeks). Human omentin-1 had no effect on body weight, heart rate, and systolic blood pressure in SHR. The measurement of isometric contraction revealed that human omentin-1 had no influence on the enhanced vasocontractile or impaired vasodilator responses in the isolated thoracic aorta from SHR. On the other hand, human omentin-1 tended to improve left ventricular diastolic failure and renal failure in SHR. In summary, human omentin-1 tended to improve hypertensive complications (heart and renal failure), while it had no influence on the severe hypertension in the aged SHR. The further study of human omentin-1 may lead to the development of therapeutic agents for hypertensive complications.
高血压是心血管疾病的主要危险因素之一,由各种异常引起,包括血管的收缩性。自发性高血压大鼠(SHR)随着年龄的增长而全身血压升高,由于几个器官受损,是研究人类原发性高血压和相关并发症的常用动物模型。人网膜素-1 是一种由 313 个氨基酸组成的脂肪细胞因子。与正常血压对照组相比,高血压患者的血清网膜素-1 水平降低。此外,网膜素-1 敲除小鼠表现出血压升高和内皮血管舒张受损。综上所述,我们假设脂肪细胞因子人网膜素-1可能改善老年 SHR(65-68 周龄)的高血压及其并发症,包括心力衰竭和肾衰竭。SHR 皮下给予人网膜素-1(18μg/kg/天,2 周)。人网膜素-1对 SHR 的体重、心率和收缩压没有影响。等长收缩的测量表明,人网膜素-1对 SHR 胸主动脉增强的血管收缩或受损的血管舒张反应没有影响。另一方面,人网膜素-1倾向于改善 SHR 的左心室舒张衰竭和肾衰竭。总之,人网膜素-1倾向于改善高血压并发症(心脏和肾衰竭),而对老年 SHR 的严重高血压没有影响。对人网膜素-1的进一步研究可能会导致治疗高血压并发症的药物的开发。