Functional and Molecular Characterization of the Endothelin System in Retinal Arterioles
Functional and Molecular Characterization of the Endothelin System in Retinal Arterioles
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DOI：
10.1167/iovs.08-3129
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发表时间：
2009-07-01
影响因子：
4.4
通讯作者：
Kuo, Lih
中科院分区：
文献类型：
--
作者：
Hein, Travis W.;Ren, Yi;Kuo, Lih
目的.内皮素（ET）系统的激活与视网膜缺血性疾病的发病机制有关。虽然ET-1，主要的内源性异构体的ET，已被证明会导致视网膜血管收缩，其合成的表达和功能的意义，以及参与特定的ET受体在视网膜小动脉仍然未知。作者研究了ET（A）和ET（B）受体及内皮素转换酶（ECE）-1在ET-1诱导的视网膜小动脉血管扩张反应中的作用。为了排除系统性混杂效应，分离猪视网膜小动脉进行血管反应性和分子研究。孤立和加压的视网膜小动脉发展的基础张力和收缩的方式依赖于浓度的ET-1。ET-1前体big ET-1引起的时间依赖性血管收缩超过20分钟，这被ECE-1抑制剂phosphoramidon阻断。ET（A）受体拮抗剂BQ 123抑制ET-1和大ET-1引起的大部分（约90%）血管收缩。ET（B）受体激动剂sarafotoxin也引起视网膜小动脉的浓度依赖性收缩，但效力显著低于ET-1。ET（B）受体拮抗剂BQ 788可阻断Sarafotoxin对血管的收缩作用，但对ET-1和big ET-1的反应仅轻微减弱。检测视网膜小动脉内皮素（A）、内皮素（B）和内皮素受体1（ECE-1）的蛋白和mRNA表达。免疫组化显示ET（A）和ET（B）受体主要分布于平滑肌，ECE-1主要分布于内皮和平滑肌。ET-1主要通过激活平滑肌ET（A）受体而引起视网膜小动脉收缩。血管内皮素受体1（ECE-1）内源性产生的ET-1足以引起视网膜小动脉内皮素（A）受体依赖性收缩。（Invest Ophthalmol维斯科学。2009;50：3329-3336）DOI：10.1167/iovs.08-3129
PURPOSE. Activation of the endothelin (ET) system has been implicated in the pathogenesis of retinal ischemic disease. Although ET-1, the predominant endogenous isoform of ET, has been shown to cause constriction of retinal vessels, the expression and functional significance of its synthesis and the involved specific ET receptors in retinal arterioles remain unknown. The authors examined the roles of ET(A) and ET(B) receptors and of endothelin-converting enzyme (ECE)-1 in ET-1-induced vasomotor responses of single retinal arterioles.METHODS. To exclude systemic confounding effects, porcine retinal arterioles were isolated for vasoreactivity and molecular studies.RESULTS. Isolated and pressurized retinal arterioles developed basal tone and constricted in a manner dependent on concentration to ET-1. ET-1 precursor big ET-1 elicited time-dependent vasoconstriction over 20 minutes, which was blocked by the ECE-1 inhibitor phosphoramidon. ET(A) receptor antagonist BQ123 inhibited most (approximately 90%) of vasoconstrictions to ET-1 and big ET-1. ET(B) receptor agonist sarafotoxin also elicited concentration-dependent constriction of retinal arterioles but with significantly less potency than ET-1. ET(B) receptor antagonist BQ788 abolished vasoconstriction to sarafotoxin but only slightly reduced responses to ET-1 and big ET-1. Protein and mRNA expressions of ET(A), ET(B), and ECE-1 were detected in retinal arterioles. Immunohistochemistry revealed ET(A) and ET(B) receptors predominantly in smooth muscle and ECE-1 predominantly in endothelium and smooth muscle.CONCLUSIONS. ET-1 elicits constriction of retinal arterioles predominantly through the activation of smooth muscle ET(A) receptors. Endogenous production of ET-1 from vascular ECE-1 is sufficient to evoke ET(A) receptor-dependent constriction in retinal arterioles. (Invest Ophthalmol Vis Sci. 2009;50:3329-3336) DOI: 10.1167/iovs.08-3129