Thrombin-Induced Responses via Protease-Activated Receptor 1 Blocked by the Endothelium on Isolated Porcine Retinal Arterioles
Thrombin-Induced Responses via Protease-Activated Receptor 1 Blocked by the Endothelium on Isolated Porcine Retinal Arterioles
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通过被内皮细胞阻断的蛋白酶激活受体 1 诱导的凝血酶在离体猪视网膜小动脉上的反应
DOI：
10.1080/02713683.2018.1496266
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发表时间：
2018
影响因子：
2
通讯作者：
Yoshida Akitoshi
中科院分区：
文献类型：
--
作者：
Takahashi Kengo;Omae Tsuneaki;Ono Shinji;Kamiya Takayuki;Tanner Akira;Yoshida Akitoshi
目的：凝血酶，一种丝氨酸蛋白酶，引起器官对血管的特异性反应。然而，凝血酶影响视网膜微循环的机制尚不清楚。我们研究了凝血酶对视网膜微血管的影响及其信号机制。方法：分离猪视网膜小动脉，插管，加压（55 cmH2O），无血流。视频显微镜技术记录了凝血酶浓度在0.001至20 mU/ml范围内的视网膜小动脉直径变化。结果：腔外给药凝血酶可诱导浓度依赖性血管反应，即低浓度小于5 mU/ml时血管收缩，高浓度大于5 mU/ml时血管松弛。然而，腔内给药凝血酶（5 mU/m）没有收缩视网膜小动脉；在脱落的血管中，腔内给药使视网膜小动脉收缩。蛋白激酶C （PKC）抑制剂和蛋白酶激活受体(PAR)-1抑制剂预处理可显著抑制凝血酶诱导的血管收缩（p< 0.01），而PAR-2和PAR-4抑制剂或剥皮对凝血酶诱导的血管收缩无显著抑制作用。与硝普钠相比，rho激酶（ROCK）抑制剂也能抑制凝血酶诱导的血管收缩（5 mU/ml）。内皮剥落和内皮型一氧化氮合酶抑制剂预处理可抑制高浓度凝血酶引起的血管松弛。结论：低浓度凝血酶通过PAR-1、PKC和ROCK引起平滑肌血管收缩，而高浓度凝血酶可能通过内皮中一氧化氮合酶的激活引起视网膜小动脉血管松弛。静脉给药时，血管内皮可能阻断凝血素诱导的视网膜小动脉收缩信号。
Purpose: Thrombin, a serine protease, causes organ-specific responses to vessels. However, the mechanism by which thrombin affects the retinal microcirculation remains unclear. We examined the effects of thrombin on the retinal microvasculature and signaling mechanisms.Methods: Porcine retinal arterioles were isolated, cannulated, and pressurized (55 cmH2O) without flow in this in vitro study. Videomicroscopy techniques recorded changes in diameter in the retinal arterioles in response to thrombin at concentrations ranging from 0.001 to 20 mU/ml.Results: Extraluminal administration of thrombin induced concentration-dependent vascular responses, that is, vasoconstriction at low concentrations less than 5 mU/ml and vasorelaxation with high concentrations greater than 5 mU/ml. However, intraluminal administration of thrombin (5 mU/m) did not constrict the retinal arterioles; in denuded vessels, intraluminal administration constricted the retinal arterioles. Thrombin-induced vasoconstriction was significantly (p< 0.01) suppressed by pretreatment with a protein kinase C (PKC) inhibitor and a protease-activated receptor (PAR)-1 inhibitor but not by PAR-2 and PAR-4 inhibitors or denudation. A rho kinase (ROCK) inhibitor also suppressed thrombin-induced vasoconstriction (5 mU/ml) compared with sodium nitroprusside. Endothelial denudation and pretreatment with an endothelial nitric oxide (NO) synthase inhibitor suppressed vasorelaxation caused by a high concentration of thrombin.Conclusions: A low concentration of thrombin causes vasoconstriction of smooth muscles via PAR-1, PKC, and ROCK, and a high concentration of thrombin possibly causes vasorelaxation of the retinal arterioles via nitric oxide synthase activation in the endothelium. The vascular endothelium might block signaling of thrombin-induced vasoconstriction in the retinal arterioles when administered intraluminally.
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新生儿凝血酶介导的肺血管舒张的受体机制。
DOI：
10.1152/ajplung.1993.265.4.l355
发表时间：
1993
期刊：
The American journal of physiology
影响因子：
--
作者：
Pinheiro,JM;Andersen,TT;Malik,AB
通讯作者：
Malik,AB
凝血酶诱导的离体脑动脉血管收缩以及合成凝血酶抑制剂的影响。
影响因子：
7.5
作者：
K. Nakamura;Y. Hatano;K. Mori
通讯作者：
K. Mori
DOI：
10.1152/ajplung.00417.2002
发表时间：
2003-08-01
影响因子：
4.9
作者：
Bogatkevich, GS;Tourkina, E;Ludwicka-Bradley, A
通讯作者：
Ludwicka-Bradley, A
蛋白激酶抑制剂抑制猪肺动脉中凝血酶诱导的收缩反应。
DOI：
--
发表时间：
1998
期刊：
Experimental and Toxicological Pathology
影响因子：
--
作者：
C. Kutz;M. Paintz;E. Glusa
通讯作者：
E. Glusa
视网膜静脉阻塞时玻璃体内凝血酶活性升高
影响因子：
1.1
作者：
T. Bertelmann;T. Stief;W. Sekundo;S. Mennel;N. Nguyen;M. Koss
通讯作者：
M. Koss