Constriction of Retinal Venules to Endothelin-1: Obligatory Roles of ETA Receptors, Extracellular Calcium Entry, and Rho Kinase.
Constriction of Retinal Venules to Endothelin-1: Obligatory Roles of ETA Receptors, Extracellular Calcium Entry, and Rho Kinase.
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DOI：
10.1167/iovs.18-25369
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发表时间：
2018-10-01
影响因子：
4.4
通讯作者：
Hein TW
中科院分区：
文献类型：
--
作者：
Chen YL;Ren Y;Xu W;Rosa RH Jr;Kuo L;Hein TW
内皮素-1（ET-1）是一种有效的血管收缩肽，与糖尿病视网膜病变和视网膜静脉阻塞等视网膜静脉病变有关。然而，导致微静脉收缩的潜在机制仍然未知。因此，我们研究了ET-1受体，细胞外钙（Ca ~（2+）），L-型电压操纵性钙通道（L-VOCCs），Rho激酶（ROCK）和蛋白激酶C（PKC）在ET-1诱导的视网膜小静脉收缩中的作用。分离猪视网膜小静脉并加压，用于使用视频显微镜技术进行血管反应性研究。使用分子工具分析蛋白质和mRNA。视网膜微静脉发展的基础张力和收缩浓度依赖于ET-1。ETA受体（ETAR）拮抗剂BQ 123可阻断ET-1对微静脉的收缩作用，而ETB受体（ETBR）拮抗剂BQ 788则无此作用。ETBR激动剂sarafotoxin S6 c不引起血管活性。在细胞外Ca ~（2+）缺乏的情况下，微静脉失去基础张力，ET-1诱导的收缩几乎被取消。虽然L-VOCC抑制剂硝苯地平也降低了基础张力，阻断了L-VOCC激活剂Bay K8644引起的血管收缩，但小静脉对ET-1的收缩仍然存在。ROCK抑制剂H-1152而不是PKC抑制剂Gö 6983阻止ET-1诱导的血管收缩。视网膜微静脉中检测到ETAR和ETBR沿着ROCK 1和ROCK 2亚型的蛋白和mRNA表达。细胞外Ca ~（2+）通过L-VOCCs内流对猪视网膜微静脉基础张力的形成和维持是必不可少的。ET-1通过激活ETAR和不依赖于L-VOCC的细胞外Ca 2+内流引起视网膜小静脉显著收缩。ROCK信号的激活，不参与PKC，似乎介导小静脉收缩，ET-1在猪视网膜。
Endothelin-1 (ET-1) is a potent vasoconstrictor peptide implicated in retinal venous pathologies such as diabetic retinopathy and retinal vein occlusion. However, underlying mechanisms contributing to venular constriction remain unknown. Thus, we examined the roles of ET-1 receptors, extracellular calcium (Ca2+), L-type voltage-operated calcium channels (L-VOCCs), Rho kinase (ROCK), and protein kinase C (PKC) in ET-1-induced constriction of retinal venules. Porcine retinal venules were isolated and pressurized for vasoreactivity study using videomicroscopic techniques. Protein and mRNA were analyzed using molecular tools. Retinal venules developed basal tone and constricted concentration-dependently to ET-1. The ETA receptor (ETAR) antagonist BQ123 abolished venular constriction to ET-1, but ETB receptor (ETBR) antagonist BQ788 had no effect on vasoconstriction. The ETBR agonist sarafotoxin S6c did not elicit vasomotor activity. In the absence of extracellular Ca2+, venules lost basal tone and ET-1–induced constriction was nearly abolished. Although L-VOCC inhibitor nifedipine also reduced basal tone and blocked vasoconstriction to L-VOCC activator Bay K8644, constriction of venules to ET-1 remained. The ROCK inhibitor H-1152 but not PKC inhibitor Gö 6983 prevented ET-1-induced vasoconstriction. Protein and mRNA expressions of ETARs and ETBRs, along with ROCK1 and ROCK2 isoforms, were detected in retinal venules. Extracellular Ca2+ entry via L-VOCCs is essential for developing and maintaining basal tone of porcine retinal venules. ET-1 causes significant constriction of retinal venules by activating ETARs and extracellular Ca2+ entry independent of L-VOCCs. Activation of ROCK signaling, without involvement of PKC, appears to mediate venular constriction to ET-1 in the porcine retina.
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DOI：
10.1186/s13167-015-0043-1
发表时间：
2015
期刊：
The EPMA journal
影响因子：
--
作者：
Flammer J;Konieczka K
通讯作者：
Konieczka K
DOI：
10.1016/bs.apha.2016.05.002
发表时间：
2016-01-01
期刊：
ENDOTHELIUM
影响因子：
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D'Orleans-Juste, P.
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10.1159/000455277
发表时间：
2017-01-01
期刊：
MACULAR EDEMA, 2ND REVISED AND EXTENDED EDITION
影响因子：
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作者：
Bandello, Francesco;Parodi, Maurizio Battaglia;Veritti, Daniele
通讯作者：
Veritti, Daniele
影响因子：
4.4
作者：
Hein, Travis W.;Rosa, Robert H., Jr.;Kuo, Lih
通讯作者：
Kuo, Lih
影响因子：
4.8
作者：
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