title: Inhibition of nitric oxide synthase with L-NAME does not increase lactate production at rest or during short-term high-intensity exercise in Thoroughbred horses.
abstract: The present study was carried out to determine whether inhibition of nitric oxide (NO) synthase promotes anaerobic metabolism in exercising horses, resulting in a significantly increased blood lactate concentration. N(omega)-nitro-L-arginine methyl ester (L-NAME) is a potent inhibitor of NO synthase that has been tested in horses and other species. Two sets of experiments, namely placebo (saline control) and L-NAME (20 mg/kg, i.v.) studies, were carried out on seven healthy, sound, exercise-trained, Thoroughbred horses in random order, 6 to 7 days apart. In both experiments, an incremental exercise protocol was used and data were obtained at rest, during submaximal exercise performed at 8 m/s on a 4.5% uphill grade, and during galloping at 14 m/s on a 4.5% uphill grade--a workload that not only elicited maximal heart rate and induced exercise-induced pulmonary haemorrhage, but also could not be sustained for more than 90 s. Measurements were also made in the recovery period. Mixed-venous blood samples, obtained at matched intervals in the two sets of experiments, were analysed in triplicate for determining the lactate concentration. Following administration of L-NAME, significant bradycardia occurred at rest (27 +/- 1 vs 37 +/- 2 beats/min in the placebo trials; p<0.0001) as well as during submaximal exercise (183 +/- 4 vs 200 +/- 4 beats/min in the placebo trials; p<0.001), but the heart rate increased during galloping at 14 m/s on a 4.5% uphill grade to reach values observed in the placebo trials (215 +/- 2 beats/min) and significant differences were not found. At rest, the mixed-venous blood lactate concentration was similar in the two experiments. With exercise, the mixed-venous blood lactate concentration increased progressively as work intensity increased in both trials, but significant differences were not found between the placebo and the L-NAME experiments during submaximal exercise, near-maximal exercise or recovery. These experiments demonstrated that inhibition of NO synthase in Thoroughbred horses does not promote enhanced anaerobic metabolism at rest or during short-term incremental exercise leading to galloping at maximal heart rate.
authors.affiliation: Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, 61802, USA. mmanohar@uiuc.edu
authors.forename: M
authors.initials: M
authors.lastname: Manohar
authors.forename: T E
authors.initials: TE
authors.lastname: Goetz
authors.forename: A S
authors.initials: AS
authors.lastname: Hassan
authors.forename: P
authors.initials: P
authors.lastname: Rothenbaum
authors.forename: S
authors.initials: S
authors.lastname: Humphrey
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004724:Endoscopy / Q000662:veterinary; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006736:Horses / Q000502:physiology*; D019344:Lactic Acid / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010805:Physical Conditioning, Animal / Q000502:physiology; D005082:Physical Exertion / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D012146:Rest / Q000502:physiology
chemical_list: D019344:Lactic Acid; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester