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The Journal of physiology1996; 495 ( Pt 3)(Pt 3); 863-874; doi: 10.1113/jphysiol.1996.sp021638

Nitric oxide and exercise in the horse.

Abstract: 1. The effects of exercise on the production rate of nitric oxide (NO) in exhaled air (VNO) and the effects of inhaled NO (80 p.p.m.) on cardiovascular and respiratory parameters were investigated in five Throughbred horses. 2. The concentration of NO ([NO]) in exhaled air collected from within the nasal opening was lower when collected at a high flow rate of 80 l min-1 than at a low flow rate of 20 l min-1: when trotting at 3.7 m s-1 the values were 0.78 +/- 0.15 and 1.23 +/- 9.14 p.p.b., respectively, and when cantering at 9 m s-1 the values were 1.69 +/- 0.31 and 2.25 +/- 0.32 p.p.b., respectively. 3. Nebulized methoxamine (40 mg ml-1 for 60 s), an alpha 1-adrenergic agonist, further reduced [NO] during the 9 m s-1 canter to 1.05 +/- 0.14 and 1.99 +/- 0.41 p.p.b. when collected at 80 and 20 l min-1, respectively, and induced cyclical changes in the breathing pattern. 4. Exercise induced a linear increase in VNO with work intensity to a maximum (428.1 +/- 31.6 pmol min-1 kg-1) which coincided with the maximal oxygen uptake for the horses (138.3 +/- 11.7 ml min-1 kg-1), although a further increase in VNO (779.3 +/- 38.4 pmol min-1 kg-1) occurred immediately after exercise. The changes in VNO correlated well with the tidal volume (r = 0.968; P < 0.01) and the haematocrit (r = 0.855; P < 0.01). 5. In the first 2 min of high intensity exercise, inhaled NO (80 p.p.m.) significantly (P < 0.05) reduced the pulmonary artery pressure: during the first minute, pulmonary artery pressure was 83.1 +/- 7.6 mmHg compared with a control value of 94.4 +/- 6.3 mmHg, and during the second minute, 84.2 +/- 7.1 mmHg compared with a control value of 98.4 +/- 4.7 mmHg. There were no other significant changes in cardiovascular or respiratory indices, including cardiac output, measured during exercise between control and inhaled NO tests. 6. The results show that exhaled NO is released from the airways of the horse and may contribute to the regulation of pulmonary vascular tone during exercise.
Publication Date: 1996-09-15 PubMed ID: 8887788PubMed Central: PMC1160787DOI: 10.1113/jphysiol.1996.sp021638Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study was an examination of the influence of physical exertion on the generation of nitric oxide in horses’ exhaled air, and the role of inhalation of nitric oxide in heart and respiratory functions. A clear increase in exhaled nitric oxide during physical activity was observed, associated with both work intensity and post-exercise tension, with inhalation of nitric oxide lessening pulmonary artery pressure.

Methodology and Findings

  • The research involved Five Thoroughbred horses participated in exercise tests to measure the production rate of Nitric Oxide (NO) in the exhaled air and the effects of inhaled NO on cardiovascular and respiratory parameters.
  • The volume of exhaled NO was tracked, and it consistently decreased at increased gas flow rates during sampling. The initial concentration of NO in exhaled air was lower when it was collected at a high flow rate than at a low flow rate. This pattern occurred in both trotting and cantering horses.
  • The use of nebulized methoxamine, an alpha1-adrenergic agonist, additionally decreased NO concentration during high-speed exercise and induced cyclical alterations in the horses’ breathing patterns.

Effects of Nitric Oxide

  • The concentration of exhaled NO (VNO) linearly increased with exercise intensity. The maximum VNO was measured immediately after exercise and was in line with the horses’ maximum oxygen uptake.
  • The changes in VNO strongly correlated with the tidal volume and the hematocrit levels.
  • A significant reduction in the pulmonary artery pressure occurred within the initial two minutes of high-intensity exercise when the horses have inhaled nitric oxide.
  • No significant alterations were recorded in the horses’ cardiovascular or respiratory indices, including cardiac output, during the exercise between the control and inhaled NO test.

End Observations

  • From the study, it was concluded that exhaled NO is released from the horses’ airways and may contribute to the regulation of pulmonary vascular tone during exercise.
  • These findings imply that closer surveillance of horses’ nitric oxide levels, particularly in athletic horse training programs, could provide useful insights into their cardio-pulmonary responses and overall performance.

Cite This Article

APA
Mills PC, Marlin DJ, Demoncheaux E, Scott C, Casas I, Smith NC, Higenbottam T. (1996). Nitric oxide and exercise in the horse. J Physiol, 495 ( Pt 3)(Pt 3), 863-874. https://doi.org/10.1113/jphysiol.1996.sp021638

Publication

ISSN: 0022-3751
NlmUniqueID: 0266262
Country: England
Language: English
Volume: 495 ( Pt 3)
Issue: Pt 3
Pages: 863-874

Researcher Affiliations

Mills, P C
  • Equine Centre, Animal Health Trust, Newmarket, UK.
Marlin, D J
    Demoncheaux, E
      Scott, C
        Casas, I
          Smith, N C
            Higenbottam, T

              MeSH Terms

              • Adrenergic alpha-Agonists / pharmacology
              • Animals
              • Blood Pressure / drug effects
              • Blood Pressure / physiology
              • Cardiovascular Physiological Phenomena
              • Female
              • Horses / physiology
              • Humans
              • Male
              • Methoxamine / pharmacology
              • Nitric Oxide / administration & dosage
              • Nitric Oxide / biosynthesis
              • Nitric Oxide / physiology
              • Physical Exertion / physiology
              • Pulmonary Artery / drug effects
              • Pulmonary Artery / physiology
              • Pulmonary Circulation / drug effects
              • Pulmonary Circulation / physiology
              • Respiration / drug effects
              • Respiration / physiology
              • Species Specificity

              References

              This article includes 49 references
              1. Wagner PD, Gillespie JR, Landgren GL, Fedde MR, Jones BW, DeBowes RM, Pieschl RL, Erickson HH. Mechanism of exercise-induced hypoxemia in horses.. J Appl Physiol (1985) 1989 Mar;66(3):1227-33.
                pubmed: 2496088doi: 10.1152/jappl.1989.66.3.1227google scholar: lookup
              2. Erickson BK, Erickson HH, Coffman JR. Pulmonary artery, aortic and oesophageal pressure changes during high intensity treadmill exercise in the horse: a possible relation to exercise-induced pulmonary haemorrhage.. Equine Vet J Suppl 1990 Jun;(9):47-52.
              3. Johns RA, Linden JM, Peach MJ. Endothelium-dependent relaxation and cyclic GMP accumulation in rabbit pulmonary artery are selectively impaired by moderate hypoxia.. Circ Res 1989 Dec;65(6):1508-15.
                pubmed: 2555077doi: 10.1161/01.res.65.6.1508google scholar: lookup
              4. Archer SL, Tolins JP, Raij L, Weir EK. Hypoxic pulmonary vasoconstriction is enhanced by inhibition of the synthesis of an endothelium derived relaxing factor.. Biochem Biophys Res Commun 1989 Nov 15;164(3):1198-205.
                pubmed: 2480112doi: 10.1016/0006-291x(89)91796-8google scholar: lookup
              5. Vane JR, Anggård EE, Botting RM. Regulatory functions of the vascular endothelium.. N Engl J Med 1990 Jul 5;323(1):27-36.
                pubmed: 2113184doi: 10.1056/NEJM199007053230106google scholar: lookup
              6. Manohar M. Tracheobronchial perfusion during exercise in ponies.. J Appl Physiol (1985) 1990 May;68(5):2182-5.
                pubmed: 2361921doi: 10.1152/jappl.1990.68.5.2182google scholar: lookup
              7. Dainty IA, McGrath JC, Spedding M, Templeton AG. The influence of the initial stretch and the agonist-induced tone on the effect of basal and stimulated release of EDRF.. Br J Pharmacol 1990 Aug;100(4):767-73.
              8. Frostell C, Fratacci MD, Wain JC, Jones R, Zapol WM. Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction.. Circulation 1991 Jun;83(6):2038-47.
                pubmed: 2040056doi: 10.1161/01.cir.83.6.2038google scholar: lookup
              9. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology.. Pharmacol Rev 1991 Jun;43(2):109-42.
                pubmed: 1852778
              10. Pepke-Zaba J, Higenbottam TW, Dinh-Xuan AT, Stone D, Wallwork J. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension.. Lancet 1991 Nov 9;338(8776):1173-4.
                pubmed: 1682593doi: 10.1016/0140-6736(91)92033-xgoogle scholar: lookup
              11. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.. Nature 1980 Nov 27;288(5789):373-6.
                pubmed: 6253831doi: 10.1038/288373a0google scholar: lookup
              12. Baile EM, Dahlby RW, Wiggs BR, Paré PD. Role of tracheal and bronchial circulation in respiratory heat exchange.. J Appl Physiol (1985) 1985 Jan;58(1):217-22.
                pubmed: 3917992doi: 10.1152/jappl.1985.58.1.217google scholar: lookup
              13. Gryglewski RJ, Palmer RM, Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor.. Nature 1986 Apr 3-9;320(6061):454-6.
                pubmed: 3007998doi: 10.1038/320454a0google scholar: lookup
              14. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor.. Nature 1987 Jun 11-17;327(6122):524-6.
                pubmed: 3495737doi: 10.1038/327524a0google scholar: lookup
              15. Gilbert IA, Fouke JM, McFadden ER Jr. Heat and water flux in the intrathoracic airways and exercise-induced asthma.. J Appl Physiol (1985) 1987 Oct;63(4):1681-91.
                pubmed: 3693204doi: 10.1152/jappl.1987.63.4.1681google scholar: lookup
              16. Gustafsson LE, Leone AM, Persson MG, Wiklund NP, Moncada S. Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans.. Biochem Biophys Res Commun 1991 Dec 16;181(2):852-7.
                pubmed: 1721811doi: 10.1016/0006-291x(91)91268-hgoogle scholar: lookup
              17. Cabanes L, Costes F, Weber S, Regnard J, Benvenuti C, Castaigne A, Guerin F, Lockhart A. Improvement in exercise performance by inhalation of methoxamine in patients with impaired left ventricular function.. N Engl J Med 1992 Jun 18;326(25):1661-5.
                pubmed: 1588979doi: 10.1056/NEJM199206183262503google scholar: lookup
              18. Foubert L, Fleming B, Latimer R, Jonas M, Oduro A, Borland C, Higenbottam T. Safety guidelines for use of nitric oxide.. Lancet 1992 Jun 27;339(8809):1615-6.
                pubmed: 1351591doi: 10.1016/0140-6736(92)91886-dgoogle scholar: lookup
              19. Wennmalm A, Benthin G, Petersson AS. Dependence of the metabolism of nitric oxide (NO) in healthy human whole blood on the oxygenation of its red cell haemoglobin.. Br J Pharmacol 1992 Jul;106(3):507-8.
              20. Hodgson DR, McCutcheon LJ, Byrd SK, Brown WS, Bayly WM, Brengelmann GL, Gollnick PD. Dissipation of metabolic heat in the horse during exercise.. J Appl Physiol (1985) 1993 Mar;74(3):1161-70.
                pubmed: 8482654doi: 10.1152/jappl.1993.74.3.1161google scholar: lookup
              21. Butler PJ, Woakes AJ, Smale K, Roberts CA, Hillidge CJ, Snow DH, Marlin DJ. Respiratory and cardiovascular adjustments during exercise of increasing intensity and during recovery in thoroughbred racehorses.. J Exp Biol 1993 Jun;179:159-80.
                pubmed: 8340728doi: 10.1242/jeb.179.1.159google scholar: lookup
              22. West JB, Mathieu-Costello O, Jones JH, Birks EK, Logemann RB, Pascoe JR, Tyler WS. Stress failure of pulmonary capillaries in racehorses with exercise-induced pulmonary hemorrhage.. J Appl Physiol (1985) 1993 Sep;75(3):1097-109.
                pubmed: 8226517doi: 10.1152/jappl.1993.75.3.1097google scholar: lookup
              23. Smith TL, Prazma J, Coleman CC, Drake AF, Boucher RC. Control of the mucosal microcirculation in the upper respiratory tract.. Otolaryngol Head Neck Surg 1993 Oct;109(4):646-52.
                pubmed: 8233499doi: 10.1177/019459989310900403google scholar: lookup
              24. Persson MG, Wiklund NP, Gustafsson LE. Endogenous nitric oxide in single exhalations and the change during exercise.. Am Rev Respir Dis 1993 Nov;148(5):1210-4.
                pubmed: 8239155doi: 10.1164/ajrccm/148.5.1210google scholar: lookup
              25. Pohl U, Wagner K, de Wit C. Endothelium-derived nitric oxide in the control of tissue perfusion and oxygen supply: physiological and pathophysiological implications.. Eur Heart J 1993 Nov;14 Suppl I:93-8.
                pubmed: 8293786
              26. Borland C, Cox Y, Higenbottam T. Measurement of exhaled nitric oxide in man.. Thorax 1993 Nov;48(11):1160-2.
                pubmed: 8296262doi: 10.1136/thx.48.11.1160google scholar: lookup
              27. Iwamoto J, Morin FC 3rd. Nitric oxide inhibition varies with hemoglobin saturation.. J Appl Physiol (1985) 1993 Nov;75(5):2332-6.
                pubmed: 8307893doi: 10.1152/jappl.1993.75.5.2332google scholar: lookup
              28. Kane DW, Tesauro T, Koizumi T, Gupta R, Newman JH. Exercise-induced pulmonary vasoconstriction during combined blockade of nitric oxide synthase and beta adrenergic receptors.. J Clin Invest 1994 Feb;93(2):677-83.
                pubmed: 7509345doi: 10.1172/JCI117020google scholar: lookup
              29. Gerlach H, Rossaint R, Pappert D, Knorr M, Falke KJ. Autoinhalation of nitric oxide after endogenous synthesis in nasopharynx.. Lancet 1994 Feb 26;343(8896):518-9.
                pubmed: 7906764doi: 10.1016/s0140-6736(94)91465-6google scholar: lookup
              30. Nelin LD, Moshin J, Thomas CJ, Sasidharan P, Dawson CA. The effect of inhaled nitric oxide on the pulmonary circulation of the neonatal pig.. Pediatr Res 1994 Jan;35(1):20-4.
              31. Bigatello LM, Hurford WE, Kacmarek RM, Roberts JD Jr, Zapol WM. Prolonged inhalation of low concentrations of nitric oxide in patients with severe adult respiratory distress syndrome. Effects on pulmonary hemodynamics and oxygenation.. Anesthesiology 1994 Apr;80(4):761-70.
              32. Johnson RL Jr, Hsia CC. Functional recruitment of pulmonary capillaries.. J Appl Physiol (1985) 1994 Apr;76(4):1405-7.
                pubmed: 8045811doi: 10.1152/jappl.1994.76.4.1405google scholar: lookup
              33. Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls.. Cell 1994 Sep 23;78(6):915-8.
                pubmed: 7522969doi: 10.1016/0092-8674(94)90266-6google scholar: lookup
              34. Trolin G, Andén T, Hedenstierna G. Nitric oxide (NO) in expired air at rest and during exercise.. Acta Physiol Scand 1994 Jun;151(2):159-63.
              35. Roos CM, Rich GF, Uncles DR, Daugherty MO, Frank DU. Sites of vasodilation by inhaled nitric oxide vs. sodium nitroprusside in endothelin-constricted isolated rat lungs.. J Appl Physiol (1985) 1994 Jul;77(1):51-7.
                pubmed: 7961274doi: 10.1152/jappl.1994.77.1.51google scholar: lookup
              36. Iwamoto J, Pendergast DR, Suzuki H, Krasney JA. Effect of graded exercise on nitric oxide in expired air in humans.. Respir Physiol 1994 Aug;97(3):333-45.
                pubmed: 7973137doi: 10.1016/0034-5687(94)90069-8google scholar: lookup
              37. Koizumi T, Gupta R, Banerjee M, Newman JH. Changes in pulmonary vascular tone during exercise. Effects of nitric oxide (NO) synthase inhibition, L-arginine infusion, and NO inhalation.. J Clin Invest 1994 Dec;94(6):2275-82.
                pubmed: 7527429doi: 10.1172/JCI117590google scholar: lookup
              38. Bauer JA, Wald JA, Doran S, Soda D. Endogenous nitric oxide in expired air: effects of acute exercise in humans.. Life Sci 1994;55(24):1903-9.
                pubmed: 7990650doi: 10.1016/0024-3205(94)00522-2google scholar: lookup
              39. Cremona G, Wood AM, Hall LW, Bower EA, Higenbottam T. Effect of inhibitors of nitric oxide release and action on vascular tone in isolated lungs of pig, sheep, dog and man.. J Physiol 1994 Nov 15;481 ( Pt 1)(Pt 1):185-95.
                pubmed: 7853241doi: 10.1113/jphysiol.1994.sp020429google scholar: lookup
              40. Zapol WM, Hurford WE. Inhaled nitric oxide in adult respiratory distress syndrome and other lung diseases.. Adv Pharmacol 1994;31:513-30.
                pubmed: 7873435doi: 10.1016/s1054-3589(08)60639-0google scholar: lookup
              41. Manohar M. Pulmonary vascular pressures of thoroughbreds increase rapidly and to a higher level with rapid onset of high-intensity exercise than slow onset.. Equine Vet J 1994 Nov;26(6):496-9.
              42. Cremona G, Higenbottam T, Takao M, Hall L, Bower EA. Exhaled nitric oxide in isolated pig lungs.. J Appl Physiol (1985) 1995 Jan;78(1):59-63.
                pubmed: 7713844doi: 10.1152/jappl.1995.78.1.59google scholar: lookup
              43. Persson MG, Lönnqvist PA, Gustafsson LE. Positive end-expiratory pressure ventilation elicits increases in endogenously formed nitric oxide as detected in air exhaled by rabbits.. Anesthesiology 1995 Apr;82(4):969-74.
              44. West JB, Mathieu-Costello O. Stress failure of pulmonary capillaries as a limiting factor for maximal exercise.. Eur J Appl Physiol Occup Physiol 1995;70(2):99-108.
                pubmed: 7768245doi: 10.1007/BF00361536google scholar: lookup
              45. Grimminger F, Spriestersbach R, Weissmann N, Walmrath D, Seeger W. Nitric oxide generation and hypoxic vasoconstriction in buffer-perfused rabbit lungs.. J Appl Physiol (1985) 1995 Apr;78(4):1509-15.
                pubmed: 7615463doi: 10.1152/jappl.1995.78.4.1509google scholar: lookup
              46. Lundberg JO, Farkas-Szallasi T, Weitzberg E, Rinder J, Lidholm J, Anggåard A, Hökfelt T, Lundberg JM, Alving K. High nitric oxide production in human paranasal sinuses.. Nat Med 1995 Apr;1(4):370-3.
                pubmed: 7585069doi: 10.1038/nm0495-370google scholar: lookup
              47. Maroun MJ, Mehta S, Turcotte R, Cosio MG, Hussain SN. Effects of physical conditioning on endogenous nitric oxide output during exercise.. J Appl Physiol (1985) 1995 Oct;79(4):1219-25.
                pubmed: 8567565doi: 10.1152/jappl.1995.79.4.1219google scholar: lookup
              48. Manohar M. Effects of glyceryl trinitrate (nitroglycerin) on pulmonary vascular pressures in standing thoroughbred horses.. Equine Vet J 1995 Jul;27(4):275-80.
              49. Dinh Xuan AT, Chaussain M, Regnard J, Lockhart A. Pretreatment with an inhaled alpha 1-adrenergic agonist, methoxamine, reduces exercise-induced asthma.. Eur Respir J 1989 May;2(5):409-14.
                pubmed: 2759222

              Citations

              This article has been cited 4 times.
              1. Wilkens HL, Neudeck S, Kästner SBR. Nasal and tracheobronchial nitric oxide production and its influence on oxygenation in horses undergoing total intravenous anaesthesia. BMC Vet Res 2022 Apr 11;18(1):134.
                doi: 10.1186/s12917-022-03234-3pubmed: 35410207google scholar: lookup
              2. Poole DC, Erickson HH. Exercise-induced pulmonary hemorrhage: where are we now?. Vet Med (Auckl) 2016;7:133-148.
                doi: 10.2147/VMRR.S120421pubmed: 30050846google scholar: lookup
              3. Araneda OF, Carbonell T, Tuesta M. Update on the Mechanisms of Pulmonary Inflammation and Oxidative Imbalance Induced by Exercise. Oxid Med Cell Longev 2016;2016:4868536.
                doi: 10.1155/2016/4868536pubmed: 26881028google scholar: lookup
              4. Rodzyń I, Karpińska K, Bis-Wencel H, Wlazło Ł, Ossowski M, Strzelec K, Jaguszewski S, Nowakowicz-Dębek B. Exposure to chemical pollutants and biological aerosol in indoor facilities for recreational and sport horses. BMC Vet Res 2024 Feb 28;20(1):78.
                doi: 10.1186/s12917-024-03930-2pubmed: 38413934google scholar: lookup