The temporal correlation between the upregulation of nos and the development of hypoxic pulmonary hypertension in rat

Alteration of nitric oxide (NO) signalling has been hypothesized to have an etiologic role in development of hypoxic pulmonary hypertension. However, regulation of expression of NO synthase (NOS) in hypoxic lungs remains controversial. This study used Northern and Western analyses for the quantitation of NOS mRNA and protein expression, lung histology together with measurements of lung and heart weights for monitoring the pulmonary vascular remodeling, and immunohistochemistry for the localization of NOS proteins. The result demonstrates an upregulation of endothelial NOS mRNA and protein in the pulmonary vascular endothelium which is temporally correlated with the vascular remodeling in the course of development of hypoxic pulmonary hypertension. Hypoxia also induced brain NOS in bronchial epithelium and inducible NOS (iNOS) in vascular smooth muscle, but did not affect the expression of iNOS in macrophages or the basal guanylyl cyclase activity in the lung. These findings showed that upregulaton of NOS was an important pathophysiological change in pulmoanry circulation which was tightly related with the vascular remodeling induced by hypoxia, suggesting strongly a role for NO in the development of pulmonary hypertension.