Mild Hyperhomocysteinemia Impairs Energy Production Efficiency but Not Exercise Capacity in Pregnant Rats. Role of Superoxide, NO and the NADPH Oxidase

Defects in the expression of eNOS increases whole‐body oxygen consumption (Vo 2 ) and substrate use during exercise. During pregnancy, hyperhomocysteinemia (HHcy) stimulates NADPH oxidase superoxide (O 2 •− ) production. This study assessed mechanisms and impact of HHcy on exercise in pregnant rats. Pregnant rats were fed methionine (9g/L) in drinking water from pregnancy day 1 to day 20 to increase plasma homocysteine (3.0±1.2 to 14.6±8.9 μM). Rats were treadmill‐tested to measure whole‐body Vo 2 . When the maximum Vo 2 , Vco 2 and RER were corrected to per work (vertical distance run × body weight) unit, Vo 2 was increased, and Vco 2 and RER were decreased in HHcy mothers. The exercise capacity was not impaired in HHcy mothers. Vo 2 of skeletal muscle was measured in vitro. NO agonist bradykinin‐induced reduction in gastrocnemius muscle Vo 2 was impaired by 55% in HHcy mothers. The response was restored in the presence of NADPH oxidase inhibitor Apocynin, or superoxide dismutase, Tiron. O 2 •− production measured by lucigenin chemiluminescence was elevated by 45% in HHcy rat, and Nitrate/Nitrite production was not affected. These results suggest that the efficiency of energy production from substrates in skeletal muscle is impaired by HHcy during pregnancy, and this is probably due to decreased NO bioavailability through NADPH oxidase generated O 2 •− . Supported by HL 43023