Interaction between endogenous nitric oxide and carbon monoxide in the pathogenesis of hypoxic pulmonary hypertension

Hypoxic pulmonary hypertension, an important pathophysiological process in the development of a vari-ety of clinical cardiac and pulmonary diseases, has critical influence on the proceeding and prognosis of the dis- eases1]. It is important to clarify the pathogenesis of the diseases. The discoveries of endogenous gas signal mole-cules, nitric oxide (NO) and carbon monoxide (CO), have been moving the research of hypoxic pulmonary hyper-tension to a very new phase. Our foregoing experiments …

Interaction between endogenous nitric oxide and carbon monoxide in the pathogenesis of hypoxic pulmonary hypertension

The aim of the study was to investigate the in-teraction between nitric oxygenase (NOS)/ nitric oxide (NO) and heme oxygenase (HO)/ carbon monoxide (CO) system in the pathogenesis of hypoxic pulmonary hypertension. On a rat model of hypoxic pulmonary hypertension, the pulmo-nary artery pressure was measured, and NO formation and expression of NOS in pulmonary tissues were examined after treatment with ZnPP-IX, an HO-1 inhibitor. The pulmonary artery pressure, CO formation and expression of HO-1 in pulmonary tissues were examined after treatment with L-NAME, a NOS inhibitor. We found that pulmonary hy-pertension developed after 2-week hypoxia, while the con-centration of NO in the pulmonary tissue homogenates and the expression of NOS in intrapulmonary artery endothelial cells decreased markedly. ZnPP-IX worsened pulmonary hypertension of hypoxic rats. However, it increased endoge-nous production of NO and the expression of NOS obviously. The concentration of CO in the pulmonary tissue homoge-nates and the expression of HO-1 in intrapulmonary artery smooth muscle cells increased markedly with hypoxic pul-monary hypertension. L-NAME worsened pulmonary hy-pertension of hypoxic rats, but inhibited CO formation and HO-1 expression (P < 0.01). The results of this study sug-gested that endogenous NOS/NO and HO/CO systems might interact with each other and therefore play an important regulating role in hypoxic pulmonary hypertension.