Objective:To investigate the effects of chronic sodium nitrite treatment on rats with high pulmonary blood flow and pulmonary hypertension and to explore its mechanism in order to provide references for the treatment of pulmonary arterial hypertension.Methods:Fifty healthy male sprague-dawley rats were randomly assigned into 5 groups(n =10):the sham group(group S)

the PAH group(group P)

the sodium nitrite group(group N)

the sodium nitrite +xanthine oxidase(XOR) inhibitor group(group NX) and the XOR inhibitor group(group X). A left-to-right shunt pulmonary hypertension model was established via an arterial-venous shunt surgery

creating a shunt between the abdominal aorta and the inferior vena cava in all groups except group S. After 11 weeks

sodium nitrite was administered(6 mg/kg)once per day for 21 days in group N and group NX. Allopurinol(30 mg/kg)

which is a XOR inhibitor

was administered in group X and in group NX one hour before sodium nitrite administration. The same volume saline was given in group S and group P. At the end of the 14 weeks

the mean arterial pressure(MAP)and the mean pulmonary artery pressure(m PAP)were monitored. The hearts were weighted to calculate right ventricular hypertrophy index(RVHI):the weight ratio of the right ventricle mass to left ventricle plus septum mass(RV/LV+IS). The NO contents in serum and lung homogenate were determined by Nitrate reductase method. The structures in pulmonary arteries were examined in goptical microscope. The endothelial nitric oxide synthase(e NOS)and XOR contents in lung tissues were measured by using Western blot. Results:Shunting of the abdominal aorta and inferior vena cava resulted in a significant increase in pulmonary artery pressures. The intragastric administration of sodium nitrite(6 mg/kg)and XOR inhibitor resulted in a significant reduction of the m PAP in PAH models. Compared with animals that received no inhibitors

the use of inhibitors caused no significant change in the m PAP. There was no significant difference in MAP in the five groups. Rats with high pulmonary blood flow and pulmonary hypertension had significantly higher RV/LV+IS weights than the sham operation rats. The rats with high pulmonary blood flow and pulmonary hypertension that were treated with intragastrically administered sodium nitrite(6 mg/kg for 21days)had significantly lower RV/LV+S weights than untreated rats with high pulmonary blood flow and pulmonary hypertension. Compared with animals that received no inhibitors

the use of inhibitors caused no significant changes in RV/LV+IS weights. Compared with that of group S

the serum NO level decreased in group P and group NX(P<0.05). Compared with that of group P

the serum NO level increased in group N(P<0.05). NO levels in the lung tissue decreased in groups NX(P<0.05). The histological analysis of sections from the left lower lung lobe revealed the development of medial hypertrophy in the small pulmonary arteries from animals with high pulmonary blood flow and pulmonary hypertension. Treatment with 6 mg/kg of intragastrically administered sodium nitrite daily for 21 days resulted in a reduction in the extent of medial hypertrophy in the small pulmonary arteries in comparison with the vessels from untreated animals with high pulmonary blood flow and pulmonary hypertension. Western blot revealed that e NOS/GAPDH and XOR/GAPDH ratios of group P were significantly lower than those of group S(P<0.05). However

the XOR/GAPDH ratios of the sodium nitrite-treated groups were significantly increased. The XOR/GAPDH ratio was significantly decreased in groups NX. Conclusion:These data suggest that long term administration of sodium nitrite improves the hemodynamics in rats with high pulmonary blood flow and pulmonary hypertension and attenuates pulmonary vascular remodeling induced by pulmonary hypertension

but the mechanism of sodium nitrite that underlies this effect requires further study.