Increased nitric oxide (no) in monocrotaline pulmonary hypertension

Excess NO is associated with a number of pathophysiological processes. We hypothesize that NO with accompanying cytotoxic redox products induce structural changes such as vascular remodeling. Methods: Rats were injected with monocrotaline (MCT, 60 mg/kg sc, n=6) 14 days prior to studies or served as controls (n=6). Isolated lungs were perfused (60 ml/min/kg) with buffer+3.5% albumin with meclofenamate (20×10^-6 M). NO was measured in expired gas (chemiluminescence) and in perfusate (hemoglobin assay). Cryostat sections were stained for eNOS. Results: MCT raised baseline PAP (P<0.005) without RV hypertrophy (RV/LV+S). NO in expired gas and perfusate were elevated (P<0.05) in treated lungs. eNOS was present in small pulmonary arteries of treated lungs but absent in control lungs. Baseline PAP RV/(LV+S) Exp. Gas NO Perfusate NO (cm H₂O) (ppb) (nmole/m) Control 9.8±.4 0.272±.007 7.1±1.5 2.6±0.6 MCT 12.6±0.4 0.282±0.007 10.9±1.9 4.7±0.3 Conclusions: Upregulation of eNUS and increased production of NO accompany monocrotaline injection prior to overt RV hypertrophy, consistent with hypothesis.