The role of adenosine in the respiratory and cardiovascular response to systemic hypoxia in the rat.

1. In rats anaesthetized with Saffan we have studied the effects of the adenosine receptor antagonists, theophylline and 8-phenyltheophylline, upon the respiratory and cardiovascular responses evoked by 5 min periods of systemic hypoxia. 2. In the group of animals that were to receive theophylline (15 mg kg-1 i.v.), arterial O2 pressure (Pa,O2) fell from 83 +/- 2 mmHg during air breathing to 38 +/- 3 or 34 +/- 3 mmHg during the 5th minute of two different control periods of hypoxia, while in the group that were to receive 8-phenyltheophylline (10 mg kg-1 i.v.), Pa,O2 fell from 83 +/- 1 to 53 +/- 2 mmHg. Neither drug significantly altered the levels of Pa,O2 reached during hypoxia. 3. During the control periods of hypoxia respiration increased, but the increase evoked at the 5th minute was significantly less than that evoked at the 2nd minute of hypoxia. This secondary waning of the hyperventilation was abolished by both drugs. 4. Similarly, both drugs attenuated the tendency for the hypoxia-induced tachycardia to wane between the 2nd and 5th minute. 5. Further, both drugs substantially reduced both the hypoxia-induced fall in arterial pressure and the increases in vascular conductance in hindlimb muscle, carotid vasculature and kidney. 6. Thus, we propose that in the rat the release of adenosine by hypoxic tissues makes a major contribution to the secondary decrease in respiration and heart rate that occurs during systemic hypoxia and to the accompanying vasodilatation in muscle and fall in arterial pressure. The effects of the adenosine antagonists on the carotid and renal vasculature are more equivocal and may be partly explained as a smaller autoregulatory dilatation to a smaller fall in systemic arterial pressure. 7. These results and proposals are discussed in relation to the conditions that are known to cause release of adenosine and in relation to its known effects upon the respiratory and cardiovascular systems.