灌注猪眼中眼微循环的内皮依赖性调节：一氧化氮和内皮素的作用

Endothelium-dependent regulation of the ophthalmic microcirculation in the perfused porcine eye: role of nitric oxide and endothelins.

作者信息

Meyer P, Flammer J, Lüscher T F

机构信息

Department of Research, University Hospital, Basel, Switzerland.

出版信息

Invest Ophthalmol Vis Sci. 1993 Dec;34(13):3614-21.

PMID:8258520

Abstract

PURPOSE

The endothelium produces nitric oxide and endothelin (ET). This study was designed to investigate the endothelium-dependent regulation of the porcine ophthalmic microcirculation.

METHODS

Isolated porcine eyes were perfused with a modified Langendorff setup (Hugo Sachs Elektronik KG, Freiburg, Germany) at a perfusion pressure of 80 cm H2O with Krebs-Ringer bicarbonate solution (37 degrees C; 95% O2, 5% CO2).

RESULTS

The inhibitor of nitric oxide formation, L-nitroarginine methylester (L-NAME; 10(-6) to 10(-4) M), evoked decreases in flow (maximal decrease, 39% +/- 6%; P < 0.005 versus control). The endothelium-dependent vasodilator bradykinin evoked increases in ophthalmic flow (maximal increase, 26% +/- 2%; P < 0.05 versus control) prevented by L-NAME. The effect of endothelin-1 (ET-1; 10(-12) to 10(-11) M) on flow was biphasic, with early vasodilation (1 to 2 minutes) and late vasoconstriction. At 10(-12) M, the increase in flow was most pronounced (24% +/- 5%; P < 0.05 versus control), whereas 10(-10) M caused only significant decreases in flow (59% +/- 5%; P < 0.001 versus control). Endothelin-3 (ET-3) evoked similar vasodilator effects as ET-1 but less vasoconstriction. The vasodilator effects of ET-3 were prevented by pretreatment of the eye with indomethacin (10(-5) M, to block the production of prostaglandins; P < 0.05 versus control). The endothelinA receptor antagonist FR-139317 significantly reduced vasoconstriction to ET-1 (10(-10) M; P < 0.001 versus control). The thromboxane analogue (U-46619) reduced flow in a concentration-dependent manner (P < 0.001 versus control).

CONCLUSIONS

Endothelium-derived nitric oxide released under basal conditions or stimulated by bradykinin significantly regulated flow to the porcine ophthalmic microcirculation. This vasodilator system may play an important protective role against vasospasm. In contrast, ET-1 has vasodilator effects through the release of prostaglandins and potent vasoconstrictor properties mediated through ETA receptors.

摘要

目的

内皮细胞可产生一氧化氮和内皮素（ET）。本研究旨在探讨猪眼微循环的内皮依赖性调节。

方法

采用改良的Langendorff装置（德国弗莱堡的Hugo Sachs Elektronik KG公司），以80 cm水柱的灌注压力，用 Krebs-Ringer碳酸氢盐溶液（37℃；95% O₂，5% CO₂）灌注离体猪眼。

结果

一氧化氮生成抑制剂L-硝基精氨酸甲酯（L-NAME；10⁻⁶至10⁻⁴ M）可引起血流量减少（最大减少39%±6%；与对照组相比，P<0.005）。内皮依赖性血管舒张剂缓激肽可引起眼血流量增加（最大增加26%±２%；与对照组相比，P<0.05），L-NAME可阻断此效应。内皮素-1（ET-1；10⁻¹²至10⁻¹¹ M）对血流量的影响呈双相性，早期血管舒张（1至2分钟）而后血管收缩。在10⁻¹² M时，血流量增加最为明显（24%±5%；与对照组相比，P<0.05），而10⁻¹⁰ M仅引起血流量显著减少（59%±5%；与对照组相比，P<0.001）。内皮素-3（ET-3）引起的血管舒张效应与ET-1相似，但血管收缩作用较弱。用吲哚美辛（10⁻⁵ M，以阻断前列腺素生成；与对照组相比，P<0.05）预处理眼可阻断ET-3的血管舒张效应。内皮素A受体拮抗剂FR-139317可显著减轻对ET-1（10⁻¹⁰ M）的血管收缩反应（与对照组相比，P<0.001）。血栓素类似物（U-46619）以浓度依赖性方式减少血流量（与对照组相比，P<0.001）。