Patients with peripheral artery disease (PAD) frequently have walking impairment due to lower extremity claudication. Our preliminary results in a rat model of aging indicate that a program of daily calf muscle stretching improves endothelium-dependent dilation of soleus muscle arterioles and increases soleus muscle blood flow during exercise. However, the effects of muscle stretching on the function of arteries supplying the legs of PAD patients is unknown. We hypothesized that daily calf muscle stretching improves vascular endothelial function and walking distance in PAD patients. To test our hypothesis, a randomized, non-blinded, crossover study was performed. Four weeks of muscle stretching (30 min/d, 5 days/wk) and 4 weeks of sedentary lifestyle (no stretching) were performed in random order. Thirteen patients with PAD participated in this study (71 ± 2 years old; 7 males and 6 females). During the stretching intervention both ankle joints were maintained at 15o of dorsiflexion using ankle dorsiflexion splints to stretch their calf muscles at home. Flow-mediated dilation (FMD; dilation to post-occlusion reactive hyperemia) and nitroglycerin-induced dilation (dilation to sublingual 0.4 mg nitroglycerin) of the popliteal artery were measured after 4 weeks of muscle stretching and after the no stretching period using ultrasound. A six-minute walk test was also performed to obtain walking distance. After 4 weeks of muscle stretching, FMD and 6-minute walking distance significantly improved as compared to the values measured after 4 weeks of no stretching (FMD: 5.2 ± 0.6 % vs. 3.7 ± 0.4 %, P=0.003 stretching vs. no stretching, 6-minute walking distance: 355 ± 32 m vs. 311 ± 31 m, P=0.007, stretching vs. no stretching; mean ± SE). No difference in nitroglycerin-induced dilation was found between groups (10.9 ± 1.4 vs. 9.9 ± 1.1 %, P=0.54, stretching vs. no stretching). Percentage change of walking distance (%change = [(stretching - no stretching) / no stretching] x 100) significantly correlated with the %change of FMD (R
2
=0.65, P=0.03). These results indicate that static calf muscle stretching enhances vascular endothelial function of the popliteal artery, contributing to improvement of walking tolerance in PAD patients.
Characteristic Analysis of Trigonelline Contained in Raphanus sativus Cv. Sakurajima Daikon and Results from the First Trial Examining Its Vasodilator Properties in Humans