Role of endothelium in vasomotor responses to endothelin system and protein kinase C activation in porcine retinal arterioles.
Role of endothelium in vasomotor responses to endothelin system and protein kinase C activation in porcine retinal arterioles.
复制标题
内皮细胞在猪视网膜小动脉内皮素系统血管舒缩反应和蛋白激酶 C 激活中的作用。
DOI：
10.1167/iovs13-13178
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发表时间：
2013
影响因子：
4.4
通讯作者：
Hein,TravisW
中科院分区：
文献类型：
--
作者：
Potts,LukeB;Bradley,PatrickD;Xu,Wenjuan;Kuo,Lih;Hein,TravisW
目的：内皮细胞分别从一氧化氮合酶（eNOS）和内皮素转换酶-1（ECE-1）合成舒张血管的一氧化氮（NO）和收缩血管的内皮素-1（ET-1）。蛋白激酶C（PKC）和Rho激酶（ROCK）是介导血管收缩的主要信号分子。尽管内皮细胞表达eNOS、ECE-1、内皮素B（ET B）受体、PKC和ROCK，但它们对ET-1诱导的血管收缩的影响仍不清楚。我们研究了这些内皮信号分子是否调节视网膜小动脉对ET-1的收缩。分离猪视网膜小动脉并加压，在内皮完整或剥脱的条件下，使用视频显微镜技术进行血管扩张研究。有或无内皮的视网膜小动脉具有相似的静息张力（最大直径的约45%）。内皮剥脱使ET-1前体大ET-1引起的血管收缩减弱约50%，但不影响ET-1、ET B激动剂sarafotoxin S6 c或PKC激活剂佛波醇-12，13-二丁酸酯（PDBu）引起的血管收缩。ROCK抑制剂H-1152引起血管舒张，并且不依赖于内皮而消除ET-1和PDBu引起的血管收缩。L-型电压操纵性钙通道（L-VOCC）阻断剂硝苯地平，PDBu-induced血管收缩被取消，并转换为NO介导的血管舒张内皮细胞的存在。ET-1诱导的血管收缩不受血流升高时内皮释放NO的影响。内皮和平滑肌ECE-1对视网膜小动脉中血管活性ET-1的合成有同等的贡献，内皮ET B受体在对ET-1的血管收缩中具有名义上的作用。当平滑肌收缩被L-VOCC阻断时，PKC激活导致内皮依赖性NO介导的血管舒张。内皮细胞和NO似乎在调节ROCK依赖性血管收缩中具有适度的作用，并且不足以对抗ET-1和PKC激活的平滑肌收缩。
Purpose.: Endothelial cells synthesize vasodilator nitric oxide (NO) and vasoconstrictor endothelin-1 (ET-1) from NO synthase (eNOS) and endothelin-converting enzyme-1 (ECE-1), respectively. Protein kinase C (PKC) and Rho kinase (ROCK) are major signaling molecules mediating vasoconstriction. Although endothelial cells express eNOS, ECE-1, endothelin B (ET B) receptors, PKC, and ROCK, their influences on ET-1–induced vasoconstriction remain elusive. We studied whether these endothelial signaling molecules modulate retinal arteriolar constriction to ET-1.Methods.: Porcine retinal arterioles were isolated and pressurized for vasomotor study, under conditions with intact or denuded endothelium, using videomicroscopic techniques.Results.: Retinal arterioles developed similar resting tone (≈ 45% of maximum diameter) with or without endothelium. Endothelial denudation attenuated vasoconstriction to ET-1 precursor, big ET-1, by almost equal to 50%, but did not affect vasoconstrictions to ET-1, ET B agonist sarafotoxin S6c, or PKC activator phorbol-12, 13-dibutyrate (PDBu). The ROCK inhibitor H-1152 caused vasodilation, and abolished vasoconstrictions to ET-1 and PDBu independent of endothelium. With L-type voltage-operated calcium channel (L-VOCC) blocker nifedipine, PDBu-induced vasoconstriction was abolished and converted to NO-mediated vasodilation in the presence of endothelium. The ET-1–induced vasoconstriction was unaffected by NO released from endothelium during flow elevation.Conclusions.: Endothelial and smooth muscle ECE-1 contribute equally to synthesis of vasoactive ET-1 in retinal arterioles, with nominal role of endothelial ET B receptors in vasoconstriction to ET-1. The PKC activation leads to endothelium-dependent NO-mediated vasodilation when smooth muscle contraction is ablated by L-VOCC blockade. Endothelial cells and NO appear to have modest roles in modulating ROCK-dependent vasoconstriction, and are insufficient to counteract smooth muscle contractions to ET-1 and PKC activation.