HS releasing sodium sulfide protects against pulmonary hypertension by improving vascular responses in monocrotaline-induced pulmonary hypertension.

Pulmonary arterial hypertension is caused by complex structural and functional changes in the endothelial and smooth muscle cells of pulmonary arteries. Hydrogen sulfide (HS), a gasotransmitter, can potentially treat pulmonary hypertension by relaxing the pulmonary arteries and decreasing bronchial pressure. Although the role of HS in systemic circulation has been examined, the HS levels in pulmonary arteries, the role of HS in endothelium-dependent vasorelaxation and the L-cysteine/HS pathway in monocrotaline-induced pulmonary arterial hypertension have not been investigated. The rats were divided into control, monocrotaline, monocrotaline + NaS, and NaS groups. The right ventricular pressure and hypertrophy were evaluated. KCl, acetylcholine, and L-cysteine responses were obtained in the main pulmonary arteries by wire myograph. HS levels were measured in pulmonary arteries and lungs by methylene blue assay. Right ventricular pressure and hypertrophy were increased by monocrotaline and ameliorated by NaS. The KCl-induced contractions and relaxing responses to acetylcholine and L-cysteine in pulmonary arteries and HS production in the lungs and pulmonary arteries were significantly attenuated in the monocrotaline group and augmented in the monocrotaline + NaS group. These findings suggest that HS levels were reduced, and L-cysteine-induced and endothelium-dependent relaxations were impaired in the pulmonary arteries in monocrotaline-induced pulmonary arterial hypertension. The HS donor, NaS, prevented endothelial dysfunction and increased pulmonary artery pressure and hypertrophy. Also, NaS enhanced the L-cysteine-mediated responses and restored the diminished HS levels in pulmonary arteries and the lungs. The treatments targeting HS might be beneficial for promoting vascular alterations, i.e. endothelial dysfunction and impaired HS-mediated relaxation in pulmonary arterial hypertension.