Department of Ophthalmology, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
Exp Eye Res. 2012 Oct;103:63-70. doi: 10.1016/j.exer.2012.08.007. Epub 2012 Aug 24.
The purpose of this study was to investigate the roles of endothelium-derived factors in the retinal arteriolar responses to acute severe elevation in systemic blood pressure (BP) in cats. Acute elevation of mean arterial BP by 60% for 5 min was achieved by inflating a balloon-tipped catheter in the descending aorta. The retinal arteriolar diameter, flow velocity, wall shear rate (WSR) and blood flow (RBF) changes during BP elevation were assessed with laser Doppler velocimetry 2 h after intravitreal injections of nitric oxide (NO) synthase inhibitor l-NAME, cyclooxygenase inhibitor indomethacin, endothelin-1 receptor antagonists (BQ-123 for type A and BQ-788 for type B), or Rho kinase inhibitor fasudil. BP elevation caused a marked increase in retinal arteriolar flow velocity and WSR with slight vasoconstriction, resulting in an increase in RBF. The increases in velocity, WSR and RBF, but not diameter, were correlated with the increase in ocular perfusion pressure. With l-NAME or indomethacin, the increase in RBF upon BP elevation was significantly attenuated due to enhanced retinal arteriolar vasoconstriction. In contrast, BQ-123 and fasudil potentiated the increased RBF. BQ-788 had no effect on arteriolar diameter and hemodynamics. Our data suggest that acute elevation of BP by 60% leads to an increase in RBF due to the release of NO and prostanoids probably through a shear stress-induced vasodilation mechanism. The release of endothelin-1 and Rho kinase activation help to limit RBF augmentation by counteracting the vasodilation. It appears that the retinal endothelium, by releasing vasoactive substances, contributes to RBF regulation during acute severe elevation of systemic blood pressure.
本研究旨在探讨内皮衍生因子在猫急性严重系统性血压升高（BP）时视网膜小动脉反应中的作用。通过在降主动脉中充气球囊尖端导管，将平均动脉 BP 升高 60%持续 5 分钟，实现急性升高。在眼内注射一氧化氮（NO）合酶抑制剂 l-NAME、环氧化酶抑制剂吲哚美辛、内皮素-1 受体拮抗剂（BQ-123 用于 A 型，BQ-788 用于 B 型）或 Rho 激酶抑制剂法舒地尔后 2 小时，评估 BP 升高期间视网膜小动脉直径、血流速度、壁切变率（WSR）和血流（RBF）的变化。BP 升高引起视网膜小动脉血流速度和 WSR 的显著增加，伴有轻微的血管收缩，导致 RBF 增加。速度、WSR 和 RBF 的增加，但不是直径，与眼灌注压的增加相关。用 l-NAME 或吲哚美辛，BP 升高时 RBF 的增加由于视网膜小动脉血管收缩增强而显著减弱。相比之下，BQ-123 和法舒地尔增强了增加的 RBF。BQ-788 对小动脉直径和血液动力学没有影响。我们的数据表明，60%的 BP 急性升高导致 RBF 增加，这是由于 NO 和前列腺素的释放，可能通过剪切应力诱导的血管扩张机制。内皮素-1 的释放和 Rho 激酶的激活有助于通过对抗血管扩张来限制 RBF 的增加。似乎视网膜内皮通过释放血管活性物质，有助于在急性严重系统性血压升高期间调节 RBF。
