Des-aspartate-angiotensin I attenuates ICAM-1 formation in hydrogen peroxide-treated L6 skeletal muscle cells and soleus muscle of mice subjected to eccentric exercise

L6 skeletal muscle cells overexpressed ICAM-1 when treated with H₂O₂. Maximum effect was observed at 200 μM H₂O₂. Des-aspartate-angiotensin I (DAA-I) concentration-dependently attenuated the overexpression. Maximum attenuation occurred at 10^− 10 M DAA-I. H₂O₂ activated NFκB and its translocation into the nucleus of L6 muscle cells suggesting that NFκB mediates the H₂O₂-induced overexpression of ICAM-1. DAA-I inhibited the activation and translocation of NFκB. H₂O₂ is a major oxidant formed during skeletal muscle contraction and is implicated in oxidative stress and skeletal muscle damage in excessive unaccustomed exercise. The data show that DAA-I has antioxidant action, and its action was further investigated in the soleus muscle of mice subjected to 240 min of eccentric exercise on a rodent treadmill. The eccentric exercise induced superoxide formation and overexpression of ICAM-1 in the soleus muscle of the mice at 3 days post exercise. DAA-I (0.2 nmole/kg/day) administered orally on day 1 (pre-exercise) and 2 days post-exercise attenuated both the ROS formation and ICAM-1 overexpression. Earlier studies show that DAA-I acts as an agonist on the angiotensin AT₁ receptor and elicits responses opposing those of angiotensin II. The present and earlier findings support the recent suggestion that angiotensin II is involved in skeletal muscle damage, and curtailment of its actions via ACE inhibitors and losartan protects and improves skeletal muscle damage. These findings open up new avenues for treatment and management of skeletal muscle damage via the interventions of the renin angiotensin system.