Changes in endogenous nitric oxide and effects of inhaled nitric oxide on pulmonary artery hypertension in chronically hypoxic rats

AIM: To investigate the role of nitric oxide (NO)in the development of chronically hypoxic pulmonary artery hypertension (PAH) and the hemodynamic effects of inhaled NO on pulmonary circulation. METHODS: 67 male adult SD rats were randomly divided into 7 groups: (1) control ( n= 9);(2) chronically intermitent hypoxia (CIH, 6 h/d, 7 d/w) 1 week( n= 7); (3) CIH 2 weeks ( n= 11); (4) CIH 3 weeks ( n= 11); (5) CIH 1 week+L-NAME (NO synthase inhibitor, 30 mg/kg, by gavage, n= 10); (6)CIH 3 weeks+L-Arg (NO precursor, 10 mg/kg, by gavage, n= 9); (7) CIH 3 weeks+inhaled NO (0.0004% for 20 min, n= 10) to determine the mean pulmonary artery pressure (MPAP), weigh the right ventricle (R) and ventricular segment plus left ventricle (S+L), and calculate R/(S+L) (g/g) and R/Wt (Wt: body weight, g/kg). RESULTS: 1.MPAP increased compared with control [(3 2±0.3 ) kPa vs (1.8±0.3) kPa, P 0.01] when CIH 1 week, reaching the highest when CIH 2 weeks; R/(S+L) and R/Wt also increased notably when CIH 1 week ( P 0.01); 2. The level of plasma NO 2 -/NO 3 - elevated significantly when CIH 2 weeks, but fell when CIH 3 weeks; the content of plasma ET-1(endothelin-1) also increased significantly. The level of plasma ET-1 correlated with R/(S+L) and R/Wt, r =0 43 and 0.46, respectively, both P 0 01; 3. The level of plasma NO 2 -/NO 3 - droped 33.2 % ( P 0.01) after treatment with L-NAME, with R/(S+L) increasing 15 2 % ( P 0 05); 4. L-Arg decreased the MPAP 17.8 %( P 0 01). CONCLUSION: The endogenous NO release increases at early stage (1-2 weeks) of chronic hypoxia, but falls at the prolonged stage; the elevated level of plasma ET-1 possibly plays an important role in remodeling of chronically hypoxic pulmonary vessels and ventricle; inhaled NO significantly decreases the chronically hypoxic PAH.