Blockade of nitric oxide-induced relaxation of rabbit aorta by cysteine and homocysteine
Li, J.; Liu, X.J.; Furchgott, R.F.
Zhongguo Yao Li Xue Bao 18(1): 11-20
1997
ISSN/ISBN: 0253-9756 PMID: 10072887 Document Number: 476596
AIM: To examine the inhibition by L-cysteine (Cys) and L-homocysteine (HoCys) of NO-induced relaxation of aorta. METHODS: The tension of rabbit aortic rings in oxygenated Krebs' solution was recorded isometrically. RESULTS: Pretreatment of endothelium-denuded rings with Cys or HoCys inhibited the NO-induced increase in cGMP. The inhibitory effects of Cys or HoCys on relaxation responses to subsequent additions of NO 75 nmol cntdot L-1 gradually diminished with time, which was consistent with the loss of the sulfhydryl concentration of Cys and HoCys. Superoxide dismutase (SOD) 35 kU cntdot L-1 attenuated the relaxation. Neither boiled SOD nor catalase 100 kU cntdot L-1 antagonized the inhibitory effects of Cys. Preaddition of SOD 35 kU cntdot L-1 inhibited the reduction of cytochrome C by Cys. Increasing concentrations of SOD from 35 to 350 kU cntdot L-1 intensified the cytochrome C reduction. Addition of xanthine 300 mu-mol cntdot L-1 plus xanthine oxidase 1 U cntdot L-1 to the mixture of cytochrome C 60 mu-mol cntdot L-1 and Cys 100 mu-mol cntdot L-1 produced an additional augmentation of SOD-inhibitable reduction of cytochrome C. The rate of the reduction of cytochrome C induced by HoCys 100 mu-mol cntdot L-1 was much slower than with Cys. Addition of NO reduced the SH concentrations of both the supernatant of aortic homogenate and Cys in Krebs' solution. CONCLUSION: The inhibition by the SH compounds of NO is mediated partly by the superoxide generated by the auto-oxidation of these compounds, and partly by a direct reaction of SH groups with NO.