Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Centre of Excellence for Cardiovascular Diseases, Second University of Naples, Naples, Italy.
PLoS One. 2013 Jul 29;8(7):e69954. doi: 10.1371/journal.pone.0069954. Print 2013.
Moderate exercise training improves energetic metabolism, tissue perfusion and induces cardiac and skeletal muscle remodeling. Sildenafil, a potent phosphodiesterase-5 inhibitor used to treat erectile dysfunction, reduces infarct size and increases tissue oxygenation in experimental models of cardiovascular disease. We have evaluated the effects of prolonged moderate exercise training and a repeat administration of sildenafil on the rat gastrocnemius and cardiac muscles. Animals were divided into two groups: sedentary and trained. Each group was subdivided into animals treated with vehicle or with two doses of sildenafil (10 or 15 mg/kg/day) during the last week of training. Physical exercise did not induce cardiac hypertrophy, whereas it increased mRNA levels of the PGC-1α, HIF-1α and VEGF genes, which are involved in mitochondrial biogenesis and angiogenesis, and reduced mRNA levels of FoxO3a, MuRF-1 and Atrogin-1. Sildenafil dose-dependently promoted both angiogenesis, as shown by increased capillary density, and muscle atrophy, as shown by muscle fibre size. These effects were more pronounced in trained animals. Our data confirm the beneficial effects of a moderate and prolonged training on cardiovascular and skeletal systems and document the positive and negative effects of sildenafil on these tissues at doses higher than those used in clinical practice. This report may impact on the use of sildenafil as a substance able to influence sports performance.
适度运动训练可改善能量代谢、组织灌注，并诱导心脏和骨骼肌重塑。西地那非是一种用于治疗勃起功能障碍的强效磷酸二酯酶-5 抑制剂，可减少心血管疾病实验模型中的梗死面积并增加组织氧合。我们评估了长期适度运动训练和西地那非重复给药对大鼠比目鱼肌和心肌的影响。动物分为两组：久坐不动组和训练组。每组再分为接受 vehicle 或西地那非（10 或 15mg/kg/天）治疗的动物，在训练的最后一周。运动训练不会引起心脏肥大，但会增加与线粒体生物发生和血管生成相关的 PGC-1α、HIF-1α 和 VEGF 基因的 mRNA 水平，并降低 FoxO3a、MuRF-1 和 Atrogin-1 的 mRNA 水平。西地那非呈剂量依赖性地促进血管生成，表现为毛细血管密度增加，以及肌肉萎缩，表现为肌纤维大小减小。这些影响在训练动物中更为明显。我们的数据证实了适度和长期训练对心血管和骨骼系统的有益影响，并记录了西地那非在高于临床实践中使用的剂量下对这些组织的积极和消极影响。本报告可能会影响将西地那非作为一种能够影响运动表现的物质的使用。
