Dual effect of aminophylline on the ventilatory response to hypoxia in the rat

Male Hooded Wistar rats were exposed to three five-minute periods of hypoxia in which they breathed a gas mixture comprising 7% O2 and 93% N2. Before the second and third hypoxic exposures rats were injected (i.m.) with aminophylline (an adenosine antagonist) at a dose of 15 mg.kg-1. In control animals, hypoxia caused an increase in ventilation which was greater during the first than during the fifth minute of hypoxia. Each injection of aminophylline significantly increased ventilation in air-breathing rats. However, the first dose of the drug did not significantly alter the hypoxic ventilatory response. The second dose of aminophylline had two effects on ventilation during hypoxia. It reduced the ventilatory response during the first minute of hypoxia, and also prevented the fall in ventilation between the first and fifth minute of exposure. Ethylenediamine injections had no effect on ventilation or the responses to hypoxia. The results suggest that adenosine has a dual role in respiratory control during hypoxia, one excitatory and the other inhibitory. Although previous studies have already identified such roles for adenosine, the present study may represent the first time in which these have been demonstrated in a single animal model.