Journal of Applied Physiology, Vol 76, Issue 1 196-203, Copyright © 1994 by American Physiological Society

ARTICLES

Role of endogenous adenosine in hypoxic ventilatory response in humans: a study with dipyridamole

M. Yamamoto, M. Nishimura, S. Kobayashi, Y. Akiyama, K. Miyamoto and Y. Kawakami
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.

To examine the role of endogenous adenosine in hypoxic ventilatory response, we measured, in nine normal young adults, ventilatory responses to isocapnic progressive hypoxia and subsequent sustained hypoxia [arterial O2 saturation (SaO2); 80%, 20 min] with and without pretreatment with dipyridamole in a double-blind crossover fashion. Dipyridamole, an adenosine uptake blocker, was expected to enhance the effect of endogenous adenosine. Pretreatment with dipyridamole (0.5 mg/kg) significantly augmented the slope of the ventilatory response to isocapnic progressive hypoxia from 0.35 +/- 0.13 (SE) to 0.70 +/- 0.25 l.min-1.%fall of SaO2(-1) (P < 0.01), although there were no significant changes in resting ventilation. On the other hand, minute ventilation, when expressed as a percentage of peak ventilation, declined to 68.4 +/- 4.3% with dipyridamole at the 9-11th min of sustained hypoxia, which was significantly lower than the 90.2 +/- 8.3% with a placebo (P < 0.05), and finally reached 56.1 +/- 7.2% with dipyridamole and 78.7 +/- 9.2% with the placebo (P < 0.1) at the 18-20th min of sustained hypoxia. In an attempt to more specifically examine the role of adenosine, aminophylline (5 mg/kg), an adenosine receptor antagonist, was injected before pretreatment with dipyridamole in four subjects. Aminophylline infusion abolished or at least attenuated the effect of dipyridamole in all four subjects. These data suggest that endogenous adenosine has a modulatory role in hypoxic ventilatory response in adult humans.

This article has been cited by other articles:

				A. G. Huxtable, J. D. Zwicker, B. Y. Poon, S. Pagliardini, S. Q. Vrouwe, J. J. Greer, and G. D. Funk Tripartite Purinergic Modulation of Central Respiratory Networks during Perinatal Development: The Influence of ATP, Ectonucleotidases, and ATP Metabolites J. Neurosci., November 25, 2009; 29(47): 14713 - 14725. [Abstract] [Full Text] [PDF]

				G. Montandon, A. Bairam, and R. Kinkead Neonatal caffeine induces sex-specific developmental plasticity of the hypoxic respiratory chemoreflex in adult rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2008; 295(3): R922 - R934. [Abstract] [Full Text] [PDF]

				H. K. Eltzschig, M. Faigle, S. Knapp, J. Karhausen, J. Ibla, P. Rosenberger, K. C. Odegard, P. C. Laussen, L. F. Thompson, and S. P. Colgan Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26 Blood, September 1, 2006; 108(5): 1602 - 1610. [Abstract] [Full Text] [PDF]

				N. K. Burki, W. J. Dale, and L.-Y. Lee Intravenous adenosine and dyspnea in humans J Appl Physiol, January 1, 2005; 98(1): 180 - 185. [Abstract] [Full Text] [PDF]

				M. Tabata, H. Kurosawa, Y. Kikuchi, W. Hida, H. Ogawa, S. Okabe, Y. Tun, T. Hattori, and K. Shirato Role of GABA within the nucleus tractus solitarii in the hypoxic ventilatory decline of awake rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2001; 281(5): R1411 - R1419. [Abstract] [Full Text] [PDF]

				H. SAITO, M. NISHIMURA, H. SHINANO, H. MAKITA, I. TSUJINO, E. SHIBUYA, F. SATO, K. MIYAMOTO, and Y. KAWAKAMI Plasma Concentration of Adenosine during Normoxia and Moderate Hypoxia in Humans Am. J. Respir. Crit. Care Med., March 1, 1999; 159(3): 1014 - 1018. [Abstract] [Full Text]