JB Hu, W Li, B Zhao, WZ Li

We explored the possible role of the nitric oxide (NO) system in the development of hypoxic pulmonary hypertension. We used in situ hybridization with a digoxigenin-labelled cRNA probe for NO synthase (NOS) mRNA to detect changes in the expression of this mRNA expression in the pulmonary artery of hypoxic pulmonary hypertensive rats. Paraffin-embedded lung sections of six 2-week-old normobarbaric hypoxic rats (Wistar, O₂=10 ± 0.5) and of seven control rats were used for in situ hybridization. Cardiac catheterization was performed on the rats to obtain pulmonary haemodynamic data. The pulmonary artery systolic pressure, mean pressure and diastolic pressure were significantly increased in hypoxic rats compared to controls (3.78 ± 0.67 kPa vs 2.87 ± 0.53 kiPa, 2.80 ± 0.65 kPa vs 1.90 ± 0.47 kPa and 1.45 ± 0.36 kPa vs 0.87 ± 0.48 kPa, respectively). All lung sections of normoxic rats showed NOS mRNA expression in endothelial cells of the pulmonary and bronchial arteries; the signals were stronger in the larger, more proximal pulmonary arteries than in the periphery. Only 3/6 sections of hypoxic rats showed weak NOS mRNA signals, the rest were negative. The strength of expression of the NOS gene in the endothelial cells of the pulmonary and bronchial arteries was negatively related to pulmonary artery systolic, mean and diastolic pressure (r = -0.673, -0.569 and -0.621, respectively, P all < 0.05). These results suggest that altered expression of NOS mRNA in endothelial cells of the pulmonary artery is probably involved in the mechanisms of hypoxic pulmonary hypertension.