Andersen Charlotte U, Mulvany Michael J, Simonsen Ulf
Department of Pharmacology, Faculty of Health Sciences, University of Aarhus, 8000 Aarhus C, Denmark.
Eur J Pharmacol. 2005 Mar 7;510(1-2):87-96. doi: 10.1016/j.ejphar.2005.01.020.
The present study addressed whether combined treatment with a phosphodiesterase type 5 inhibitor, sildenafil, and a nitric oxide donor, molsidomine, prevents development of pulmonary hypertension in chronic hypoxic rats. Two weeks of hypoxia increased right ventricular systolic pressure, and right ventricular and lung weight. Treatment with either sildenafil (10 mg/kg/day) or molsidomine (15 mg/kg/day) in drinking water reduced right ventricular systolic pressure and weight, while lung weight was unchanged. Combining sildenafil and molsidomine did not have additional effects compared to molsidomine alone. The number of muscularized pulmonary arteries with diameters below 50 microm was increased in vehicle and sildenafil-treated, but not in molsidomine-treated hypoxic rats. Acetylcholine relaxation was blunted in arteries from vehicle and molsidomine-treated, but not in sildenafil-treated rats. In conclusion, both sildenafil and molsidomine blunts pulmonary hypertension and right ventricular hypertrophy in chronic hypoxic rats, but no synergistic effects were observed.
本研究探讨了5型磷酸二酯酶抑制剂西地那非与一氧化氮供体吗多明联合治疗是否可预防慢性低氧大鼠肺动脉高压的发生。两周的低氧状态增加了右心室收缩压、右心室重量和肺重量。饮用水中给予西地那非（10毫克/千克/天）或吗多明（15毫克/千克/天）治疗可降低右心室收缩压和重量，而肺重量未改变。与单独使用吗多明相比，西地那非与吗多明联合使用没有额外效果。在给予赋形剂和西地那非治疗的低氧大鼠中，直径小于50微米的肌化肺动脉数量增加，但在给予吗多明治疗的低氧大鼠中未增加。在给予赋形剂和吗多明治疗的大鼠的动脉中，乙酰胆碱舒张作用减弱，但在给予西地那非治疗的大鼠中未减弱。总之，西地那非和吗多明均可减轻慢性低氧大鼠的肺动脉高压和右心室肥厚，但未观察到协同作用。
