Nitric oxide-induced ciliary muscle relaxation during contraction with endothelin-1 is mediated through elevation of cyclic GMP

被引:12
作者
Masuda, H
Tamaoki, S
Goto, M
Ishida, A
Kamikawatoko, S
Tokoro, T
Azuma, H
机构
[1] TOKYO MED & DENT UNIV,INST MED & DENT ENGN,DEPT MED CHEM,CHIYODA KU,TOKYO 101,JAPAN
[2] TOKYO MED & DENT UNIV,INST MED & DENT ENGN,DEPT ELECT ENGN,TOKYO 101,JAPAN
[3] TOKYO MED & DENT UNIV,FAC MED,DEPT OPHTHALMOL,TOKYO 101,JAPAN
关键词
bovine ciliary muscle; cyclic GMP; endothelin-1; guanylate cyclase; sodium nitroprusside; methylene blue; IBMX; nitric oxide; relaxation;
D O I
10.1076/ceyr.16.12.1245.5025
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose. Nitric oxide (NO) relaxes ciliary smooth muscle, and endothelin-l (ET-1) is reported to regulate ciliary muscle tone. Despite the physiological significance of nitric oxide and ET-1, very few studies have attempted to characterize the mutual modes of action of these mediators in this tissue. Thus, the present experiments were designed to investigate a possible relaxation mechanism of nitric oxide in bovine ciliary muscle that has been contracted by ET-1. Methods. The effects of sodium nitroprusside (SNP), as a nitric oxide donor, methylene blue, as an inhibitor of guanylate cyclase, and 8-bromo-cyclic GMP on the bovine ciliary muscle contracted with ET-1 were examined. The changes in cyclic GMP level and relaxation, in response to SNP alone or in combination with 3-isobutyl-1-methylxanthine (IBMX) as a nonselective inhibitor of phosphodiesterases, were also determined. Results. Sodium nitroprusside (SNP) produced a concentration-dependent relaxation, which was significantly (p < 0.005) augmented by 10(-5) M 3-isobutyl-1-methylxanthine (IBMX) and significantly (p < 0.005) attenuated by 3 x 10(-5) M methylene blue as an inhibitor of guanylate cyclase. The relaxation in response to SNP was accompanied by an increase in the cyclic 3':5' guanosine monophosphate (cyclic GMP) level, which was again significantly (p < 0.05) augmented by 10(-5) M IBMX and significantly (p < 0.005) attenuated by 3 x 10(-5) M methylene blue. The exogenously applied 8-bromo-cyclic GMP relaxed the ciliary muscle strips during the contraction caused by ET-1. Conclusions. These results lead us to assume that NO generated from SNP is closely related to cyclic GMP production via the activation of guanylate cyclase and, in turn, causes a relaxation response in the bovine ciliary muscle contracted with ET-1.
引用
收藏
页码:1245 / 1251
页数:7
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