Effect of Systemic Administration of the Nitric Oxide Synthase Inhibitor L-NMMA on the Human Ventilatory Response to Hypoxia

  • Kojiro Ide
  • Matthew Worthley
  • Todd Anderson
  • Marc J. Poulin
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 605)

Although it is well known that nitric oxide (NO) production is involved in several physiological functions (e.g., vasodilatation, platelet inhibition, immune responses, cell adhesion and neurotransmission), its role in the regulation of respiration is less clear. In carotid body studies, most studies indicate that NO appears to play an inhibitory role in response to hypoxia (Gozal, Gozal, Gozal and Torres 1996a; Gozal, Torres, Gozal and Littwin 1996b; Iturriaga, Villanueva and Mosqueira 2000; Trzebski, Sato, Suzuki and Sato 1995; Valdes, Mosqueira, Rey, Del Rio and Iturriaga 2003). However, there is less agreement for studies carried out in the nucleus tractus solitarius (NTS), with some studies indicating that NO may play an excitatory role in response to hypoxia (Kline, Yang, Huang and Prabhakar 1998; Vitagliano, Berrino, D'Amico, Maione, De Novallis and Rossi 1996) and others suggesting that NO plays an inhibitory role (Haxhiu, Chang, Dreshaj, Erokwu, Prabhakar and Cherniack 1995; Ogawa, Mizusawa, Kikuchi, Hida, Miki and Shirato 1995). Further, the aforementioned studies have been carried out in experimental animal models and it is unclear whether NO is involved in the regulation of respiration in humans. Thus, we sought to elucidate the effects of systemic administration of N g -Monomethyl-L-arginine (L-NMMA) on the response of ventilation (Ve) to 20 min of isocapnic hypoxia in human volunteers.


Nitric Oxide Mean Arterial Blood Pressure Nucleus Tractus Solitarius Isocapnic Hypoxia Middle Cerebral Artery Blood Velocity 
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  1. Gozal, D., Gozal, E., Gozal, Y.M. and Torres, J.E. (1996a) Nitric oxide synthase isoforms and peripheral chemoreceptor stimulation in conscious rats. Neuroreport 7, 1145–1148.CrossRefPubMedGoogle Scholar
  2. Gozal, D., Torres, J.E., Gozal, Y.M. and Littwin, S.M. (1996b) Effect of nitric oxide synthase inhibition on cardiorespiratory responses in the conscious rat. J. Appl. Physiol. 81, 2068–2077.PubMedGoogle Scholar
  3. Haxhiu, M.A., Chang, C.H., Dreshaj, I.A., Erokwu, B., Prabhakar, N.R. and Cherniack, N.S. (1995) Nitric oxide and ventilatory response to hypoxia. Respir. Physiol. 101, 257–266.CrossRefPubMedGoogle Scholar
  4. Ide, K., Eliasziw, M. and Poulin, M.J. (2003) The relationship between middle cerebral artery blood velocity and end-tidal PCO2 in the hypocapnic-hypercapnic range in humans. J. Appl. Physiol. 95, 129–137.PubMedGoogle Scholar
  5. Iturriaga, R., Villanueva, S. and Mosqueira, M. (2000) Dual effects of nitric oxide on cat carotid body chemoreception. J. Appl. Physiol. 89, 1005–1012.PubMedGoogle Scholar
  6. Kline, D.D., Yang, T., Huang, P.L. and Prabhakar, N.R. (1998) Altered respiratory responses to hypoxia in mutant mice deficient in neuronal nitric oxide synthase. J. Physiol. 511.1, 273–287.CrossRefPubMedGoogle Scholar
  7. Ogawa, H., Mizusawa, A., Kikuchi, Y., Hida, W., Miki, H. and Shirato, K. (1995) Nitric oxide as a retrograde messenger in the nucleus tractus solitarii of rats during hypoxia. J. Physiol. 486.2, 495–504.PubMedGoogle Scholar
  8. Poulin, M.J. and Robbins, P.A. (1998) Influence of cerebral blood flow on the ventilatory response to hypoxia in humans. Experim. Physiol. 83, 95–106.Google Scholar
  9. Trzebski, A., Sato, Y., Suzuki, A. and Sato, A. (1995) Inhibition of nitric oxide synthesis potentiates the responsiveness of carotid chemoreceptors to systemic hypoxia in the rat. Neurosci. Lett. 190, 29–32.CrossRefPubMedGoogle Scholar
  10. Valdes, V., Mosqueira, M., Rey, S., Del Rio, R. and Iturriaga, R. (2003) Inhibitory effects of NO on carotid body: contribution of neural and endothelial nitric oxide synthase isoforms. Am. J. Physiol. 284, L57–L68.Google Scholar
  11. Vitagliano, S., Berrino, L., D’Amico, M., Maione, S., De Novallis, V. and Rossi, F. (1996) Involvement of nitric oxide in cardiorespiratory regulation in the nucleus tractus solitarii. Neuropharmacology 35, 625–631.CrossRefPubMedGoogle Scholar

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© Springer 2008

Authors and Affiliations

  • Kojiro Ide
  • Matthew Worthley
  • Todd Anderson
  • Marc J. Poulin

    There are no affiliations available

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