Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada, Aomori, 034-8628, Japan.
Kitasato University Veterinary Teaching Hospital, Higashi 23 Bancho 35-1, Towada, Aomori, 034-8628, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 2024 May;397(5):3379-3387. doi: 10.1007/s00210-023-02795-w. Epub 2023 Nov 13.
Hypertension is one of the major risk factors for renal failure and cardiovascular diseases, and is caused by various abnormalities including the contractility of blood vessels. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which mimic human type 2 diabetes, are frequently used to study obesity-induced insulin resistance (IR) and hypertension. Human omentin-1 is one of the recently identified adipocytokines. We previously demonstrated that human omentin-1 not only caused vasodilation in rat isolated blood vessels, but also prevented inflammatory responses, a possible mechanism relating IR, in human vascular endothelial cells. Taken together, we hypothesized that human omentin-1 may reduce obesity-induced IR and hypertension in OLETF rats.
OLETF rats were intraperitoneally administered with human omentin-1 for 7 days.
Human omentin-1 had no influence on overweight, hyperglycemia, urinary glucose extraction, hyperinsulinemia, and systemic IR in OLETF rats. Human omentin-1 decreased systolic blood pressure in OLETF rats. The measurement of isometric contraction revealed that human omentin-1 had no influence on the agonist-induced contractile and relaxant responses in isolated thoracic aorta from OLETF rats. However, the relaxant response mediated by human insulin was converted into the contractile response in thoracic aorta from OLETF rats, which was prevented by human omentin-1. The Western blotting revealed that human omentin-1 improved the decrease in endothelial nitric oxide synthase activation in isolated thoracic aorta from OLETF rats.
In summary, we for the first time revealed that human omentin-1 partly reduces vascular IR and thereby inhibits hypertension in OLETF rats.
高血压是肾衰竭和心血管疾病的主要危险因素之一，由包括血管收缩性在内的各种异常引起。模仿人类 2 型糖尿病的大坂长野肥胖（OLETF）大鼠常用于研究肥胖引起的胰岛素抵抗（IR）和高血压。人网膜素-1 是最近发现的脂肪细胞因子之一。我们之前的研究表明，人网膜素-1不仅能引起大鼠离体血管舒张，还能预防人血管内皮细胞中与 IR 相关的炎症反应，这可能是一种机制。综上所述，我们假设人网膜素-1可能会降低 OLETF 大鼠肥胖引起的 IR 和高血压。
OLETF 大鼠经腹腔注射人网膜素-1，连续 7 天。
人网膜素-1对 OLETF 大鼠超重、高血糖、尿糖提取、高胰岛素血症和全身 IR 无影响。人网膜素-1降低了 OLETF 大鼠的收缩压。等长收缩测量表明，人网膜素-1对 OLETF 大鼠胸主动脉中激动剂诱导的收缩和舒张反应没有影响。然而，人胰岛素介导的舒张反应在 OLETF 大鼠的胸主动脉中转变为收缩反应，而人网膜素-1可以预防这种反应。Western blot 分析表明，人网膜素-1改善了 OLETF 大鼠离体胸主动脉中内皮型一氧化氮合酶激活的下降。
综上所述，我们首次揭示了人网膜素-1部分减轻了 OLETF 大鼠血管 IR，从而抑制了高血压。
