Dietary nitrate dramatically increases force in mouse skeletal muscle

Abstract

Nitrate supplementation has beneficial effects on exercise performance, with both improved mitochondrial efficiency and reduced ATP cost of muscle force production implicated. It was the purpose of this study to examine if nitrate supplementation could improve Ca2+ handling and contractile function using skeletal muscles from C57bl/6 male mice given 0.1 mmol • kg−1 sodium nitrate in drinking water for 7 days (Nitrate). Age matched controls were provided water without added nitrate (Control). Myoplasmic free [Ca2+] ([Ca2+]i) was significantly elevated from 20–150 Hz stimulation in fast‐twitch muscle fibers dissected from Nitrate (n = 5) compared to Control mice (n = 7). This resulted in increased contractile force at stimulation frequencies up to 50 Hz. At 100 Hz stimulation, the rate of force development was ~35% faster in the Nitrate group. These changes were accompanied by increased expression of the Ca2+ handling proteins calsequestrin and the dihydropyridine receptor in fast‐twitch muscles of Nitrate mice. In conclusion, these results show a striking and novel effect of nitrate supplementation on intracellular Ca2+ handling and force production. These data provide a new mechanism by which nitrate can exert effects on muscle performance, and provide a potential new therapeutic role for nitrate in conditions with muscle weakness.