Abstract: Objective To investigate the effect of vardenafil on high altitude pulmonary hypertension in rats, and the possible mechanism thereof. Methods Thirty rats were randomly divided into three groups: control group with normal-pressure and normal-oxygen (group C), pulmonary hypertension group with low-pressure and low-oxygen (group P), and the group treated by vardenafil in low-pressure and low-oxygen condition (group V). The rats of group P and group V were exposed to low-pressure and low-oxygen condition in an auto-modulating hypobaric and hypoxic cabin to simulate 5 000 m high altitude environment (air pressure 50 kPa, oxygen concentration 10%) for 8 hours daily. Vardenafil (1 mg/kg) was given by gastrogavage to rats in group V once daily for 4 weeks, while the isodose distilled water was given by gastrogavage to rats in group C and group P. The mean pulmonary arterial pressure and right ventricular mass index were measured respectively
after 4-week treatment. Morphologic changes of peripheral pulmonary artery were detected by light microscope. The serum levels of nitric oxide (NO) and endothelin-1 (ET-1) were detected as well. Results The pulmonary arterial pressure and right ventricular mass index were significantly higher in group P than those of group C and group V (P < 0.05). The ratio of vascular medial wall thickness to external diameter (WT%) and the ratio of pulmonary artery wall area to tube area (WA%) were significantly increased in group P than those of group C and group V (P < 0.05). Furthermore, the serum level of NO was significantly lower in group P than that of group C and group V, but the serum level of ET-1 was significantly increased compared with that of group C and group V (P < 0.05). Conclusion Vardenafil can effectively reduce the pulmonary arterial pressure, and attenuate pulmonary vessels and right ventricle remodeling induced by high altitude pulmonary hypertension.

Key words: hypertension, pulmonary, phosphodiesterase inhibitors;nitric oxide, endothelin-1, high altitude pulmonary hypertension, vardenafil