Augmented S ‐nitrosylation contributes to impaired relaxation in angiotensin II hypertensive mouse aorta: role of thioredoxin reductase

Nitric oxide (NO) is a critical factor in the cardiovascular system and modifies target protein's cysteine residue via S ‐nitrosylation. Thioredoxin (Trx) and Trx reductase (TrxR) play a role in limiting S ‐nitrosylation. We hypothesized that S ‐nitrosylation is associated with reduced vasodilation in hypertensive mice. Aortic rings from normotensive (sham) and angiotensin II (AngII)‐induced hypertensive C57BL6 mice were treated with a TrxR inhibitor, 1‐chloro‐2,4‐dinitrobenzene (DNCB) for 30 min and relaxation to acetylcholine (ACh) was measured following contraction with phenylephrine. DNCB reduced relaxation to ACh compared with vehicle in sham aorta but not in AngII. DNCB decreased relaxation to sodium nitroprusside (SNP) in both sham and AngII aortic rings. Soluble guanylyl cyclase (sGC) activity through cyclic GMP assay was reduced by DNCB in activation status with SNP. Total protein S ‐nitrosylation was confirmed by biotin‐switch method/western blot analysis and was enhanced in AngII aorta (1.5‐fold) compared to sham. TrxR activity was inhibited in AngII aorta (0.66‐fold) compared to sham. These data suggest that increased S ‐nitrosylation is related to impaired vasodilation in AngII. Since in AngII, TrxR function was inactivated and S ‐nitrosylation was increased, TrxR could provide link between increased oxidative stress and augmented S ‐nitrosylation in AngII hypertension.