L-arginine supplementation causes additional effects on exercise-induced angiogenesis and VEGF expression in the heart and hind-leg muscles of middle-aged rats.

The effects of dietary L-arginine supplementation on exercise-induced angiogenesis and VEGF expression were examined in male middle-aged (12 months old) Wistar rats. Exercise training lasted for six weeks at 20 m/min on a 0% gradient for 10-60 min/day. Rats in the L-arginine-treated groups drank water containing 2.5% L-arginine. According to histochemical identification of the capillary profile, in the soleus muscle the capillary-to-fiber (C:F) ratio showed a significantly greater value in the L-arginine-treated training group than in both the sedentary control and training groups. Training with L-arginine significantly increased the C:F ratio in the subendocardium of the left ventricle, whereas training alone did not. In the plantaris muscle, training with or without L-arginine significantly increased the capillary density, but it did not affect the C:F ratio. A Western blot analysis showed that training with L-arginine significantly increased VEGF protein expression by 2.9-fold in the soleus muscle and by 1.7-fold in the left ventricle, but the increase with training alone was insignificant. The tissue endothelial nitric oxide synthase protein levels were significantly increased in both the soleus (by 1.3-fold) and the left ventricle (by 1.4-fold) only after training with L-arginine supplementation. In the plantaris muscle, these protein levels did not change after either training or L-arginine treatment. The present results suggest that in middle-aged rats, L-arginine administration caused additional effects on exercise-induced angiogenesis by presumably promoting VEGF expression in the hind-leg muscle as well as in the left ventricle.