Aims: 

At the beginning of exposure to hypoxia the damage of peripheral pulmonary vessels by reactive oxygen species (ROS) caused development chronic hypoxic pulmonary hypertension (HPH). Interaction of vasodilatatory nitric oxide (NO) and vasoconstrictory ROS damaging the vessels. In our experiment with chronic hypoxic adult male rats we tested part of interaction betwen NO and ROS.

Methods: 

Rats were treated with SOD mimetic -Tempol (group T) and NO/superoxide donor - Molsidomine (group M) alone and in combination (group M+T) during first 7 days of exposure to 3 weeks hypoxia. We isolated rat lungs and perfused salt solution with albumine to study haemodynamic changes of pulmonary circulation by analysis of perfusion pressure increments induced by stepwise increase flow (P/Q relationship).

Results: 

The value of Intercept of P/Q relationship was significantly reduced in all groups (T, M, M+T, C) than hypoxic group without treatment (H). Thus, basal tonus of pulmonary vessels was significantly lower in all groups than group H. The value of Slope P/Q relationship in groups treated with Molsidomine (M, M+T) was significantly higher than group H. Thus, adding Molsidomine increased upstream pressure to perfusate flow.

Conclusion: 

These results demonstrated potentiation of morphologic reconstruction of peripheral pulmonary vessels by Molsidomine. The damage of pulmonary vessels by ROS plays important role at the beginning of hypoxic pulmonary hypertension. Molsidomine alone or in a combination with Tempol cannot reduce development of HPH. Increased production ROS and consequently generation of peroxynitrite is the reason of that status.

Supported by Center MSMT 1M 0510 and grant GACR 305/05/0672.