Early Intervention is important for inhibiting pulmonary hypertension progression

Abstract

L‐arginine(L‐Arg) has been shown to attenuate pulmonary hypertension (PH). To investigate how L‐Arg affects the nitric oxide (NO) to inhibit PH, SD rats were treated with monocrotaline (MCT) once ± L‐Arg for 3 or 5 weeks (wk). The right ventricular systolic pressure (RVSP), NO level in plasma, superoxide anion (O2·−) generation in lung and pulmonary arteries wall thickness were measured. The proteins expressions and the association in lung were determined by western blot and immunoprecipitation. MCT increased RVSP, pulmonary arteries wall thickness and decreased endothial NO synthase (eNOS) and heat shock protein 90 (HSP90) expression and association, phosphorylation of eNOS at S1177 and T495. O2·− was increased at 3 wk post‐MCT but not at 5 wk post‐MCT. However, NO production was decreased at 3 wk post‐MCT and restored to control level at 5 wk post‐MCT despite progressive PH. L‐Arg can decrease RVSP, O2·− generation, pulmonary arteries wall thickness and increase NO production. L‐Arg can increase eNOS expression, phosphorylation at S1177, the association of eNOS and HSP90 at 3 wk post‐MCT but not at 5 wk post‐MCT without altering the HSP90 expression and phosphorylation at T495. Our findings indicate that L‐arg can inhibit the further development of PH despite of losing the preventive effect on protein expression and association to generate NO in late stage PH and emphasize the importance of early intervention of PH.