This study was performed to test whether
monocrotaline (MCT)-induced early airway dysfunction and gas exchange abnormalities result in arterial
hypoxemia. Thirty young male Sprague-Dawley rats were divided into four groups: control, MCT1, MCT2, and MCT3. Each of the control animals was injected (subcutaneously) with saline; each of the MCT rats was injected with MCT (60 mg/kg, subcutaneously). The rats were tested 1 (MCT1), 2 (MCT2), or 3 (MCT3) weeks after MCT injection. Two days before each animal was tested, it was anesthetized with
sodium pentobarbital, and its carotid artery was chronically cannulated. Blood was sampled from the arterial
catheter of the conscious rat, and blood
gases and pH were measured. Pulmonary arterial pressure (Ppa) was determined in the anesthetized, open chest animal. Heart weight was measured and a weight ratio obtained of right ventricle (RV) to left ventricle plus septum (LV+S). The amount of lung
substance P and airway
neutral endopeptidase (NEP) activity were also measured. MCT significantly decreased arterial
oxygen tension (Pao2) and increased the RV/(LV+S) weight ratio 2 and 3 weeks after administration, whereas it did not significantly increase Ppa until 3 weeks after injection. MCT significantly increased lung
substance P levels and decreased airway NEP activities 1-3 weeks after administration. These data suggest that
tachykinins cause
hypoxemia and RV
hypertrophy; then
hypoxia may augment the development of
pulmonary hypertension.