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.
Publication Date: 2001-08-25 PubMed ID: 11519679DOI: 10.1023/a:1010612403902Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The article presents a study that investigates whether blocking the production of nitric oxide, a molecule that plays a crucial role in many physiological processes, leads to an increase in anaerobic metabolism which would result in a higher blood lactate concentration in Thoroughbred horses. The findings suggest that inhibiting nitric oxide synthase does not lead to enhanced anaerobic metabolism at rest or during short-term high-intensity exercise.
Objective and Experimental Setup
- The objective of the study was to evaluate whether the inhibition of nitric oxide (NO) synthase leads to an increase in anaerobic, or oxygen-less, metabolism in horses, noted by an increase in blood lactate concentration.
- The inhibition of NO was achieved through the administration of L-NAME, a strong inhibitor of NO synthase.
- The experiments were performed on seven healthy, sound, exercise-trained, Thoroughbred horses in randomized order with a gap of 6 to 7 days between each experiment.
- Each set of experiments involved a control trial (saline placebo) and an L-NAME trial, where the horses were administered a dose of 20 mg/kg of L-NAME intravenously.
- The experiment sessions involved resting, submaximal exercise, and high-intensity exercise performed at different speeds and inclines, designed to induce high heart rates and exercise-induced pulmonary haemorrhage.
Measurements and Findings
- Blood samples were collected from the horses both during rest and exercise and were analyzed for lactate concentration.
- Post-administration of L-NAME, significant drops in heart rate (bradycardia) were observed at rest and during submaximal exercise. However, during high-intensity exercise, heart rates reached similar levels to those observed during the placebo trials.
- The blood lactate concentration was similar in the horses during rest in both the placebo and L-NAME trials.
- Exercise induced a progressive increase in blood lactate concentration in both trials, but there was no significant difference between the placebo and L-NAME trials during any stage of exercise or recovery.
Conclusion
- The findings suggest that inhibition of NO synthase, or the blocking of nitric oxide production, does not augment anaerobic metabolism during rest or during short-term high-intensity exercise in Thoroughbred horses.
- This implies that the regulation of NO production may not have a significant effect on the physiological metabolic responses to exercise in these animals.
Cite This Article
APA
Manohar M, Goetz TE, Hassan AS, Rothenbaum P, Humphrey S.
(2001).
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.
Vet Res Commun, 25(6), 483-494.
https://doi.org/10.1023/a:1010612403902 Publication
Researcher Affiliations
- Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, 61802, USA. mmanohar@uiuc.edu
MeSH Terms
- Animals
- Blood Pressure / drug effects
- Endoscopy / veterinary
- Female
- Heart Rate / drug effects
- Horses / physiology
- Lactic Acid / biosynthesis
- Lactic Acid / blood
- Male
- NG-Nitroarginine Methyl Ester / pharmacology
- Nitric Oxide Synthase / antagonists & inhibitors
- Physical Conditioning, Animal / physiology
- Physical Exertion / drug effects
- Physical Exertion / physiology
- Random Allocation
- Rest / physiology
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