Beraprost sodium, a stable prostacyclin analogue, elicits dilation of isolated porcine retinal arterioles: roles of eNOS and potassium channels.
Beraprost sodium, a stable prostacyclin analogue, elicits dilation of isolated porcine retinal arterioles: roles of eNOS and potassium channels.
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DOI：
10.1167/iovs.14-14902
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发表时间：
2014-07
影响因子：
4.4
通讯作者：
Shinji Ono;T. Nagaoka;Tsuneaki Omae;Ichiro Tanano;Takayuki Kamiya;Shinichi Otani;Akihiro Ishibazawa
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作者：
Shinji Ono;T. Nagaoka;Tsuneaki Omae;Ichiro Tanano;Takayuki Kamiya;Shinichi Otani;Akihiro Ishibazawa
Prostacyclin （PGI2）通常被描述为一种内源性肾上腺皮质激素衍生的松弛因子，但视网膜小动脉对PGI2的血管反应性及其潜在机制尚不完全清楚。我们使用稳定的PGI2类似物beraprost钠（BPS）检测了PGI2对视网膜微循环的影响，以及参与这种血管舒缩活性的信号机制。方法分离猪视网膜小动脉，插管，加压，体外无血流。视频显微技术记录了BPS的直径响应。结果Beraprost钠引起剂量依赖性（0.1 pM-0.1 μM）的视网膜小动脉舒张，而PGI2受体（IP）拮抗剂CAY10441可以消除这种舒张。贝拉前列素钠诱导的血管舒张作用在内皮去除后降低50%，并被一氧化氮（NO）合成酶抑制剂N(G)-硝基- l -精氨酸甲酯（L-NAME）抑制。1h -1,2,4-恶二唑[4,3- A]喹诺沙林-1- 1 （ODQ）对可溶性鸟苷环化酶的抑制作用和rp -8- br - camp对蛋白激酶A （PKA）的阻断作用与L-NAME相当。非选择性钾通道抑制剂四乙基铵和三磷酸腺苷敏感钾（KATP）通道阻滞剂格列本脲也能抑制Beraprost钠诱导的血管舒张。格列苯脲存在时残留的血管舒张随着后续使用ODQ而进一步降低。结论：作为一种稳定的PGI2类似物，贝拉前列素钠可通过IP受体介导视网膜小动脉血管舒张。目前的研究结果表明，BPS分别通过激活内皮中的PKA和激活血管平滑肌中的KATP通道诱导NO介导的内皮依赖性和非依赖性视网膜小动脉扩张。
PURPOSE Prostacyclin (PGI2) is usually described as an endoEDRFsthelium-derived relaxing factor, but the vasoreactivity to PGI2 in the retinal arterioles and the underlying mechanisms are not fully understood. We examined the effects of PGI2 on the retinal microcirculation using beraprost sodium (BPS), a stable PGI2 analogue, and the signaling mechanisms involved in this vasomotor activity. METHODS Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded the diametric responses to BPS. RESULTS Beraprost sodium elicited dose-dependent (0.1 pM-0.1 μM) vasodilation of the retinal arterioles that was abolished by the PGI2 receptor (IP) antagonist CAY10441. Beraprost sodium-induced vasodilation decreased by 50% after the endothelium was removed and was inhibited by the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) comparable with denudation. Inhibition of soluble guanylyl cyclase by 1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and blockage of protein kinase A (PKA) by Rp-8-Br-cAMPS were comparable to L-NAME. Beraprost sodium-induced vasodilation was also inhibited by the nonselective potassium channel inhibitor, tetraethylammonium, and the adenosine triphosphate-sensitive potassium (KATP) channel blocker, glibenclamide. Residual vasodilation in the presence of glibenclamide decreased further with subsequent application of ODQ. CONCLUSIONS Beraprost sodium, a stable PGI2 analogue, causes vasodilation of the retinal arterioles mediated via the IP receptor. The current findings suggest that BPS elicits endothelium-dependent and -independent dilation of the retinal arterioles mediated by NO induced by activation of PKA in the endothelium and the KATP channel activation in the vascular smooth muscle, respectively.