S-Nitroso-L-Cysteine Ameliorated Pulmonary Hypertension in the MCT-Induced Rats through Anti-ROS and...

Area of Science:

• Cardiovascular Research
• Pulmonary Medicine
• Pharmacology

Background:

• Pulmonary hypertension (PH) is a severe condition characterized by high pulmonary artery pressure (PAP) and vascular remodeling.
• While inhaled nitric oxide (NO) is used clinically, the therapeutic potential of its endogenous derivatives, like S-nitrosothiols (SNO), remains largely unexplored.
• Previous work indicated S-nitroso-L-cysteine (CSNO) inhibits RhoA activity, suggesting benefits for vasodilation and vascular remodeling.

Purpose of the Study:

• To investigate the therapeutic effects of inhaled CSNO on established pulmonary hypertension (PH) in a rat model.
• To elucidate the molecular mechanisms underlying CSNO's action in PH, focusing on signaling pathways, oxidative stress, and endoplasmic reticulum stress.

Main Methods:

• Pulmonary hypertension was induced in rats using monocrotaline (MCT).
• Inhaled CSNO was administered to assess its effects on PAP, right ventricular (RV) hypertrophy, and cardiac fibrosis.
• Molecular analyses included evaluating STAT3 and ERK pathway activation, smooth muscle protein expression, endoplasmic reticulum (ER) stress, mitophagy, and reactive oxygen species (ROS) production in lung tissues and in vitro.

Main Results:

• Inhaled CSNO significantly attenuated elevated PAP and ameliorated RV hypertrophy and fibrosis in MCT-induced PH rats.
• CSNO administration inhibited the hyperactivation of STAT3 and ERK signaling pathways in the lungs of PH rats.
• The treatment also normalized smooth muscle protein expression, reduced aberrant ER stress and mitophagy, and inhibited ROS production in vitro.

Conclusions:

• CSNO demonstrates significant therapeutic potential for pulmonary hypertension by promoting pulmonary artery relaxation and regulating vascular remodeling.
• Its mechanisms involve anti-oxidative stress and anti-inflammatory pathways, including the inhibition of ROS, STAT3, and ERK signaling.
• CSNO represents a promising therapeutic candidate for treating PH.