Nitric oxide synthase inhibition speeds oxygen uptake kinetics in horses during moderate domain running.
Abstract: Within the moderate exercise intensity domain, the speed of oxygen uptake (V(O(2))) kinetics at the transition to a higher metabolic rate is thought to be limited by an inertia of the oxidative machinery. Nitric oxide (NO)-induced inhibition of O(2) consumption within the electron transport chain may contribute to this inertia. This investigation tested the hypothesis that a reduction or removal of any such NO effect via infusion of N(omega)-nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor) would speed V(O(2)) kinetics at the onset of moderate exercise. Five Thoroughbred geldings underwent four transitions to running speeds of 7 m sec(-1) (two control, C, 2 L-NAME [20 mg kg(-1)]) on an equine treadmill during which pulmonary gas exchange was determined using a bias flow system. Consistent with exercise in the moderate intensity domain, in none of the transitions was a V(O(2)) slow component elicited. The L-NAME treatment significantly accelerated V(O(2)) kinetics via a reduction of the primary amplitude time constant (C, 17.3 +/- 1.7; L-NAME, 11.8 +/- 1.5 sec, P < 0.05) concomitant with faster overall dynamics (i.e. T(50) and T(75) both P < 0.05) and a trend toward a decreased O(2) deficit (C, 6.4 +/- 0.7; L-NAME, 4.7 +/- 1.2 L; P = 0.06). These data support the notion that NO contributes prominently to the oxidative enzyme inertia and thus the speed of V(O(2)) kinetics at the onset of moderate intensity exercise in the horse.
Publication Date: 2002-08-06 PubMed ID: 12161330DOI: 10.1016/s1569-9048(02)00068-xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research investigates whether inhibiting Nitric oxide synthase (NOS), an enzyme responsible for nitric oxide production, can speed up the uptake of oxygen in horses during moderate-intensity exercise. The study results indicate that blocking nitric oxide production through the introduction of N(omega)-nitro-L-arginine methyl ester (L-NAME) increases the speed of oxygen uptake, which suggests a significant role of nitric oxide in controlling the rate of oxygen consumption under these conditions.
Understanding Nitric Oxide (NO) and Oxygen Uptake Kinetics
- Nitric oxide (NO) contributes significantly to the inertia of oxidative machinery, causing a delay in the onset of oxygen consumption (V(O(2))) as the metabolic rate increases during moderate exercise intensity.
- Oxygen uptake kinetics refer to how quickly the body can absorb and utilize oxygen, particularly during physical activity. Faster V(O(2)) kinetics enable quicker adaptation to exercise.
Experimental Design and Execution
- The experiment involved five Thoroughbred geldings that underwent four transitions to a running speed of 7 m per second, including two control phases and two phases involving the introduction of L-NAME, an NOS inhibitor.
- The pulmonary gas exchanges of the horses were monitored using a bias flow system across these different phases. The transitions did not result in a V(O(2)) slow component, indicating that the exercise was kept within the moderate intensity domain.
Significant Findings
- Introduction of L-NAME significantly expedited V(O(2)) kinetics — the rate at which the horse’s body absorbed and utilized oxygen. This was evidenced by a reduction in the primary amplitude time constant and faster overall dynamics for oxygen uptake.
- The study also observed a trend towards a decreased oxygen deficit with the L-NAME treatment, although this was not significant at the P < 0.05 level.
Implications
- The experiment underscores the prominent role played by NO in oxygen uptake kinetics during moderate intensity exercise.
- The findings could potentially lead to the development of new strategies for enhancing athletic performance in horses and other large animals by manipulating NO levels.
Cite This Article
APA
Kindig CA, McDonough P, Erickson HH, Poole DC.
(2002).
Nitric oxide synthase inhibition speeds oxygen uptake kinetics in horses during moderate domain running.
Respir Physiol Neurobiol, 132(2), 169-178.
https://doi.org/10.1016/s1569-9048(02)00068-x Publication
Researcher Affiliations
- Department of Anatomy, Kansas State University, 228 Coles Hall, 1600 Denison Avenue Manhattan, KS 66506-5802, USA. ckindig@ucsd.edu
MeSH Terms
- Analysis of Variance
- Animals
- Enzyme Inhibitors / pharmacology
- Exercise Test
- Horses / physiology
- Lactic Acid / blood
- Male
- Matched-Pair Analysis
- NG-Nitroarginine Methyl Ester / pharmacology
- Nitric Oxide Synthase / antagonists & inhibitors
- Oxygen / pharmacokinetics
- Oxygen Consumption / drug effects
- Respiration / drug effects
- Running / physiology
Grant Funding
- HL-50306 / NHLBI NIH HHS
Citations
This article has been cited 15 times.- Jones AM. Dietary nitrate supplementation and exercise performance.. Sports Med 2014 May;44 Suppl 1(Suppl 1):S35-45.
- Hirai DM, Copp SW, Ferguson SK, Holdsworth CT, Musch TI, Poole DC. The NO donor sodium nitroprusside: evaluation of skeletal muscle vascular and metabolic dysfunction.. Microvasc Res 2013 Jan;85:104-11.
- Hirai DM, Copp SW, Ferguson SK, Holdsworth CT, McCullough DJ, Behnke BJ, Musch TI, Poole DC. Exercise training and muscle microvascular oxygenation: functional role of nitric oxide.. J Appl Physiol (1985) 2012 Aug 15;113(4):557-65.
- Murias JM, Spencer MD, Kowalchuk JM, Paterson DH. Muscle deoxygenation to VO₂ relationship differs in young subjects with varying τVO₂.. Eur J Appl Physiol 2011 Dec;111(12):3107-18.
- Murias JM, Kowalchuk JM, Paterson DH. Speeding of VO2 kinetics with endurance training in old and young men is associated with improved matching of local O2 delivery to muscle O2 utilization.. J Appl Physiol (1985) 2010 Apr;108(4):913-22.
- Gurd BJ, Peters SJ, Heigenhauser GJ, LeBlanc PJ, Doherty TJ, Paterson DH, Kowalchuk JM. Prior heavy exercise elevates pyruvate dehydrogenase activity and speeds O2 uptake kinetics during subsequent moderate-intensity exercise in healthy young adults.. J Physiol 2006 Dec 15;577(Pt 3):985-96.
- McDonough P, Jones AM, Poole DC. Nitric oxide and muscle VO2 kinetics.. J Physiol 2006 Jun 1;573(Pt 2):565-6; author reply 567-8.
- Grassi B, Hogan MC, Kelley KM, Howlett RA, Gladden LB. Effects of nitric oxide synthase inhibition by L-NAME on oxygen uptake kinetics in isolated canine muscle in situ.. J Physiol 2005 Nov 1;568(Pt 3):1021-33.
- Wilkerson DP, Rittweger J, Berger NJ, Naish PF, Jones AM. Influence of recombinant human erythropoietin treatment on pulmonary O2 uptake kinetics during exercise in humans.. J Physiol 2005 Oct 15;568(Pt 2):639-52.
- Kindig CA, Stary CM, Hogan MC. Effect of dissociating cytosolic calcium and metabolic rate on intracellular PO2 kinetics in single frog myocytes.. J Physiol 2005 Jan 15;562(Pt 2):527-34.
- Wilkerson DP, Campbell IT, Jones AM. Influence of nitric oxide synthase inhibition on pulmonary O2 uptake kinetics during supra-maximal exercise in humans.. J Physiol 2004 Dec 1;561(Pt 2):623-35.
- Jones AM, Wilkerson DP, Campbell IT. Nitric oxide synthase inhibition with L-NAME reduces maximal oxygen uptake but not gas exchange threshold during incremental cycle exercise in man.. J Physiol 2004 Oct 1;560(Pt 1):329-38.
- Jones AM, Koppo K, Wilkerson DP, Wilmshurst S, Campbell IT. Dichloroacetate does not speed phase-II pulmonary VO2 kinetics following the onset of heavy intensity cycle exercise.. Pflugers Arch 2004 Mar;447(6):867-74.
- Jones AM, Koppo K, Burnley M. Effects of prior exercise on metabolic and gas exchange responses to exercise.. Sports Med 2003;33(13):949-71.
- Jones AM, Wilkerson DP, Koppo K, Wilmshurst S, Campbell IT. Inhibition of nitric oxide synthase by L-NAME speeds phase II pulmonary .VO2 kinetics in the transition to moderate-intensity exercise in man.. J Physiol 2003 Oct 1;552(Pt 1):265-72.
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