**Conflict of interest**

*Vascular Biology - Selection of Mechanisms and Clinical Applications*

consumes H2O2 to form sulfenic acid, then subsequently disulfide bond [115]. Glutathione (GSH) peroxidase 1 uses the similar mechanism to inactivate H2O2, superoxide, and ONOO<sup>−</sup> in the presence of the tripeptide compound GSH. A prospective cohort study showed that reduced levels of GSH peroxidase 1 were

Another effective antioxidative method is to protect redox-sensitive molecules from being oxidized. In the body, the thiol group on GSH can form reversible mixed disulfide bonds with cellular proteins under oxidative stress conditions. These disulfide bonds can be broken by the enzyme glutaredoxin when the surrounding cell environment reverts back to its normal state [80, 117]. The addition of scavengers to directly remove ROS/RNS can also restore the nitroso-redox balance. An example is the elimination of superoxide by ascorbic acid (vitamin C) [113]. By limiting

This may explain the success of the clinical trial of combining nitrate drug isosorbide dinitrate with hydralazine, a NADPH oxidase inhibitor, where heart failure was reduced by 45% [118]. By inhibiting superoxide generation from NADPH oxidase,

The high concentrations of NO can be controlled through scavenging NO via oxyhemoglobin in red blood cells and myoglobin in the skeletal and heart muscle. These two proteins react with NO to form nitrate, which is considered as the primary method for inactivating NO in the cardiovascular system [119]. Hemoglobin and myoglobin can also scavenge ONOO<sup>−</sup> by their metal centers, generating nitrate

We briefly reviewed the molecular mechanisms of muscle contraction and relaxation in the cardiovascular system and highlighted the importance of physiological and pathological effects of NO and oxidative stress. NO and ROS both determine the structural integrity and functionality of the cardiovascular system. The cardiovascular system not only nourishes cells, but also provides paths for immune response and systematic signaling. Drugs are transported by this system to the correct site for metabolic reactions. Tissue regeneration also relies on a healthy

OH and ONOO<sup>−</sup>.

associated with increased mortality in coronary disease patients [116].

*Maintenance of redox balance in the cardiovascular system.*

superoxide, other reactive species can also be repressed, such as •

ONOO<sup>−</sup> level may be reduced and NO function preserved.

**16**

from the reactions [120].

**Figure 5.**

**6. Conclusions and future outlooks**

The authors have declared that no conflict of interest exists.
