Interaction of nitric oxide and reactive oxygen species in the development of hypoxic pulmonary hypertension

Abstract

Chronic hypoxia damages peripheral pulmonary vessels and causes hypoxic pulmonary hypertension (HPH). According to our hypothesis, the release of reactive oxygen species (ROS), nitric oxide (NO) and products of their interaction contribute to the pathogenesis of HPH. Experimenting with chronic hypoxic adult male rats, we tested the effect of NO and ROS interaction. Hypoxic rats were treated solely with SOD mimetic Tempol (group T, n=6) and NO donor Molsidomine (group M, n=9) or in combination (group MT, n=6) during first 7 days of exposure to 3 weeks hypoxia (FiO2=0.1). Seven untreated hypoxic rats (group H) and seven normoxic controls (group C) were used.Pulmonary artery blood pressure (PAP), and the weight of RV, LV+S were measured. PAP was significantly decreased in group M (P<0.05) and group T (P<0.05) but not in group MT compared with group H. In all hypoxic groups the right‐to‐left heart weight ratio was significantly increased compared to group C, and groups receiving Tempol (T, MT) had significantly (P<0.01 and P<0.01 respectively) less increase in weight of RV or whole heart compared with group H.Molsidomine or Tempol added alone (but not in combination) at the beginning of exposure to chronic hypoxia reduces HPH. Tempol alone or in a combination reduces of hypoxia‐induced right heart hypertrophy.Supported by Cardiovascular Research Center MSMT 1M 0510, Grants: GACR 305/05/0672 and GAUK 7780/2007