Nitric oxide synthase inhibition in Thoroughbred horses augments O2 extraction at rest and submaximal exercise, but not during short‐term maximal exercise

Abstract

Work is required to establish the role of endogenous nitric oxide (NO) in metabolism of resting and exercising horses. To examine the effects of NO synthase inhibition on O2 extraction and anaerobic metabolism at rest, and during submaximal and maximal exertion. Placebo and NO synthase inhibition (with Nomega-nitro-L-arginine methyl ester [L-NAME] administered at 20 mg/kg bwt i.v.) studies were performed in random order, 7 days apart on 7 healthy, exercise-trained Thoroughbred horses at rest and during incremental exercise leading to 120 sec of maximal exertion at 14 m/sec on a 3.5% uphill grade. At rest, NO synthase inhibition significantly augmented the arterial to mixed-venous blood O2 content gradient and O2 extraction as mixed-venous blood O2 tension and saturation decreased significantly. While NO synthase inhibition did not affect arterial blood-gas tensions in exercising horses, the exercise-induced increment in haemoglobin concentration and arterial O2 content was attenuated. In the L-NAME study, during submaximal exercise, mixed-venous blood O2 tension and haemoglobin-O2 saturation decreased to a greater extent causing O2 extraction to increase significantly. During maximal exertion, arterial hypoxaemia, desaturation of haemoglobin and hypercapnia of a similar magnitude developed in both treatments. Also, the changes in mixed-venous blood O2 tension and haemoglobin-O2 saturation, arterial to mixed-venous blood O2 content gradient, O2 extraction and markers of anaerobic metabolism (lactate and ammonia production, and metabolic acidosis) were not different from those in the placebo study. Endogenous NO production augments O2 extraction at rest and during submaximal exertion, but not the during short-term maximal exercise. Also, NO synthase inhibition does not affect anaerobic metabolism at rest or during exertion. It is unlikely that endogenous NO release modifies aerobic or anaerobic metabolism in horses performing short-term maximal exertion.