El-Galaly A, Aalkjaer C, Kringelholt S K, Misfeldt M W, Bek T
Department of Ophthalmology, Aarhus University Hospital, 8000 Aarhus C, Denmark.
Institute of Biomedicine (Physiology), Aarhus University, 8000 Aarhus C, Denmark.
Exp Eye Res. 2014 Nov;128:67-72. doi: 10.1016/j.exer.2014.09.006. Epub 2014 Sep 20.
The carbonic anhydrase inhibitor dorzolamide can induce relaxation of retinal arterioles with a consequent increase in blood flow and oxygenation of the retina. It has been shown that the mechanisms underlying this relaxation are independent of extracellular acidosis and CO2. The purpose of the present study was to investigate the possible involvement of nitric oxide (NO) and intracellular acidosis in dorzolamide-induced relaxation of retinal arterioles. Porcine retinal arterioles were mounted in a wire myograph and dorzolamide induced relaxation was studied after 1) the addition of the NO synthase inhibitor l-NAME (3 × 10(-4) M) or the guanylyl cyclase inhibitor ODQ (3 × 10(-6) M), and 2) after loading the smooth muscle cells with the pH sensitive fluorophore SNARF-1-AM and studying changes in vascular tone and intracellular fluorescence after the induction of hypoxia, addition of lactate (10(-2) M), and extracellular acidification (pH = 7.0) alone and in the presence of dorzolamide (10(-3) M). Dorzolamide significantly relaxed retinal arterioles (p < 0.03), and the effect was significantly higher in the presence of perivascular tissue than in isolated vessels at the highest concentration (p < 0.01). In the presence of perivascular tissue dorzolamide-induced relaxation could be reduced by NO inhibition (p < 0.02). Dorzolamide increased intracellular acidification (p < 0.02) during extracellular acidosis, but there was no relation between relaxation and intracellular acidosis. In conclusion, dorzolamide-induced vasorelaxation depends on NO and the perivascular retinal tissue, but is independent of acidification in the extracellular and the intracellular space of retinal vascular smooth muscle cells. Other factors than NO and acidification are involved in dorzolamide-induced relaxation of retinal arterioles.
碳酸酐酶抑制剂多佐胺可诱导视网膜小动脉舒张，进而增加视网膜的血流量和氧合作用。研究表明，这种舒张作用的机制与细胞外酸中毒和二氧化碳无关。本研究的目的是探讨一氧化氮（NO）和细胞内酸中毒在多佐胺诱导的视网膜小动脉舒张中可能发挥的作用。将猪视网膜小动脉安装在钢丝肌动描记器上，在以下情况下研究多佐胺诱导的舒张作用：1）添加一氧化氮合酶抑制剂L-NAME（3×10⁻⁴ M）或鸟苷酸环化酶抑制剂ODQ（3×10⁻⁶ M）后；2）用pH敏感荧光团SNARF-1-AM加载平滑肌细胞后，在诱导缺氧、添加乳酸（10⁻² M）以及单独和在多佐胺（10⁻³ M）存在下进行细胞外酸化（pH = 7.0）后，研究血管张力和细胞内荧光的变化。多佐胺可显著舒张视网膜小动脉（p < 0.03），在最高浓度下，有血管周围组织时的舒张效果显著高于分离的血管（p < 0.01）。在有血管周围组织存在时，多佐胺诱导的舒张作用可因NO抑制而减弱（p < 0.02）。在细胞外酸中毒期间，多佐胺会增加细胞内酸化（p < 0.02），但舒张作用与细胞内酸中毒之间没有关联。总之，多佐胺诱导的血管舒张依赖于NO和视网膜血管周围组织，但与视网膜血管平滑肌细胞细胞外和细胞内空间的酸化无关。除了NO和酸化外，还有其他因素参与多佐胺诱导的视网膜小动脉舒张。
