Blockade of nitric oxide-induced relaxation of rabbit aorta by cysteine and homocysteine

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.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.L-1 attenuated
the inhibition by Cys and HoCys of NO-induced relaxation. Neither boiled SOD nor
catalase 100 kU.L-1 antagonized the inhibitory effects of Cys. Preaddition of SOD
35 kU.L-1 inhibited the reduction of cytochrome C by Cys. Increasing
concentrations of SOD from 35 to 350 kU.L-1 intensified the cytochrome C
reduction. Addition of xanthine 300 mumol.L-1 plus xanthine oxidase 1 U.L-1 to
the mixture of cytochrome C 60 mumol.L-1 and Cys 100 mumol.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 mumol.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.