Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
Invest Ophthalmol Vis Sci. 2013 Jul 10;54(7):4586-94. doi: 10.1167/iovs.13-11756.
Adiponectin, an important adipocytokine secreted by adipocytes, has anti-inflammatory and atheroprotective effects on vascular tissue via the adiponectin receptor (adipoR). However, the action of adiponectin in the retinal microcirculation is unknown. We examined the direct effect and underlying mechanism of the vasomotor action of adiponectin in porcine retinal arterioles.
Porcine retinal arterioles (internal diameter, 60-90 μm) were isolated, cannulated, and pressurized (55 cmH2O) without flow in this in vitro study. Videomicroscopic techniques were used to record changes in diameter in response to adiponectin.
The retinal arterioles dilated in a dose-dependent (0.125-7.5 μg/mL) manner in response to adiponectin. The vasodilation decreased significantly after removal of the endothelium. N(G)-nitro-L-arginine methyl ester (a nitric oxide [NO] synthase inhibitor), 1H-1,2,4-oxadia-zolo[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor), but not wortmannin (a phosphatidylinositol 3-kinase inhibitor) inhibited the effect of adiponectin-induced vasodilation comparable with that of denudation. Pretreatment with compound C, an activated protein kinase (AMPK) inhibitor, partially but significantly reduced vasodilation. Incubation with GW6471, a peroxisome proliferator-activated receptor blocker, did not significantly inhibit vasodilation by adiponectin. AdipoR1 and adipoR2 immunoreactions were observed in the endothelium of retinal arterioles.
Adiponectin elicits mainly endothelium-dependent dilation of the retinal arterioles. Endothelium-dependent vasodilation likely induced by adiponectin results from NO via activation of guanylyl cyclase that is partially dependent on AMPK activity. Understanding the effect of adiponectin on the retinal vasculature may help improve potential therapies for retinal vascular disorders, especially diabetic retinopathy in patients with type 2 diabetes mellitus.
脂联素是一种由脂肪细胞分泌的重要脂肪细胞因子，通过脂联素受体（adipoR）对血管组织具有抗炎和抗动脉粥样硬化作用。然而，脂联素在视网膜微循环中的作用尚不清楚。我们研究了脂联素在猪视网膜小动脉中舒血管作用的直接作用和潜在机制。
在这项离体研究中，分离并套管用微管夹夹住猪视网膜小动脉（内径 60-90μm），在无血流的情况下加压至 55cmH2O。使用视频显微镜技术记录对脂联素的直径变化反应。
视网膜小动脉呈剂量依赖性（0.125-7.5μg/ml）扩张。去除内皮后，血管舒张明显减少。N(G)-硝基-L-精氨酸甲酯（一氧化氮[NO]合酶抑制剂）、1H-1,2,4-oxadia-zolo[4,3-a]quinoxalin-1-one（可溶性鸟苷酸环化酶抑制剂），而不是wortmannin（一种磷酸肌醇 3-激酶抑制剂），可抑制脂联素诱导的血管舒张作用，与去内皮作用相当。用激活蛋白激酶（AMPK）抑制剂化合物 C 预处理可部分但显著减少血管舒张。用过氧化物酶体增殖物激活受体阻滞剂 GW6471 孵育不能显著抑制脂联素引起的血管舒张。在视网膜小动脉的内皮中观察到脂联素受体 1 和脂联素受体 2 的免疫反应。
脂联素引起视网膜小动脉主要依赖内皮的舒张。脂联素引起的内皮依赖性血管舒张可能是通过激活鸟苷酸环化酶引起的，NO 部分依赖于 AMPK 活性。了解脂联素对视网膜血管的作用可能有助于改善潜在的视网膜血管疾病治疗方法，特别是 2 型糖尿病患者的糖尿病视网膜病变。
