Kotikoski Hanna, Vapaatalo Heikki, Oksala Olli
Institute of Biomedicine, Biomedicum Helsinki, Pharmacology, University of Helsinki, Helsinki, Finland.
Curr Eye Res. 2003 Feb;26(2):119-23. doi: 10.1076/ceyr.26.2.119.14511.
Nitric oxide (NO) may control intraocular pressure (IOP)-regulating mechanisms physiologically and in ocular diseases such as glaucoma. The aim of the present study was to clarify whether an increase in aqueous humor outflow facility could explain the IOP-lowering effect of the NO/cyclic GMP pathway we recently described.
Test compounds were administered to anesthetized rabbits (New Zealand White, n = 6) intracamerally (5 microl) in the following doses: nitrosocaptopril 12.3 microg, captopril 10.9 microg, sodium nitroprusside (SNP) 13.1 microg and 8-Br-cGMP 22.3 microg. Outflow facility (C) was determined by the two-level constant pressure infusion method. Outflow facility, C( 1) and C(2), was measured at lower and higher pressure levels, respectively.
Outflow facility was increased after treatment with SNP (increase in C in the experimental eye as compared to the control eye C( 1) 80% and C(2) 74%), nitrosocaptopril (C(1) 69% and C(2) 64%) and 8-Br-cGMP (C(1) 35% and C(2) 33%). Captopril had no effect on outflow facility (C(1) -12% and C(2) 2%). Blood pressure was not affected by the drugs.
We conclude that enhancement of outflow facility by nitrosocaptopril, SNP and 8-Br-cGMP, their second messenger derivative, at least partly explains the IOP-lowering effect of NO releasing compounds.
一氧化氮（NO）可能在生理状态下以及青光眼等眼部疾病中控制眼压（IOP）调节机制。本研究的目的是阐明房水流出易度的增加是否可以解释我们最近描述的NO/环鸟苷酸途径的降眼压作用。
将受试化合物以以下剂量经前房内（5微升）给予麻醉的家兔（新西兰白兔，n = 6）：亚硝基卡托普利12.3微克、卡托普利10.9微克、硝普钠（SNP）13.1微克和8-溴环鸟苷酸22.3微克。采用两级恒压灌注法测定流出易度（C）。分别在较低和较高压力水平下测量流出易度C(1)和C(2)。
用SNP（与对照眼相比，实验眼C(1)增加80%，C(2)增加74%）、亚硝基卡托普利（C(1)增加69%，C(2)增加64%）和8-溴环鸟苷酸（C(1)增加35%，C(2)增加33%）处理后，流出易度增加。卡托普利对流出易度无影响（C(1)降低12%，C(2)增加2%）。血压不受这些药物影响。
我们得出结论，亚硝基卡托普利、SNP及其第二信使衍生物8-溴环鸟苷酸对流出易度的增强作用至少部分解释了释放NO化合物的降眼压作用。
