A study on rats of the effects of chronic hypoxia from birth on respiratory and cardiovascular responses evoked by acute hypoxia

Abstract

1. Comparative studies were performed on eighteen rats 54 days old made chronically hypoxic from birth in an hypoxic chamber at 12% O2 (CHB), and in eight weight-matched control rats (NB, 42 days old); both CHB and NB rats were anaesthetized with Saffan. 2. In NB rats, breathing 12 or 8% O2 for 5 min induced a pattern of response comparable to that described in older rats (10-11 weeks old): an initial increase and secondary fall in minute volume (VE), a fall in arterial pressure (ABP), an increase in muscle vascular conductance, while cerebral blood flow (CBF) increased at the 1st minute in six animals and fell by the 5th minute in all animals. The adenosine receptor antagonist 8-phenyl-theophylline (8-PT, 10 mg kg-1) reduced the secondary fall in VE, the fall in ABP and muscle vasodilatation, indicating they were partly mediated by adenosine. 3. In CHB rats breathing 12% O2, VE was higher (277 +/- 12 vs. 204 +/- 18 ml min-1), arterial partial pressures of O2 (45 +/- 2 vs. 88 +/- 3 mmHg), CO2 (32 +/- 1 vs. 44 +/- 1 mmHg) and ABP (105 +/- 5 vs. 131 +/- 5 mmHg) were lower, while muscle vascular conductance was higher (0.08 +/- 0.01 vs. 0.03 +/- 0.01 ml min-1 mmHg-1) than in NB rats breathing air; these differences were reduced, but not abolished, when CHB rats acutely breathed air for 5 min. 4. In CHB rats, the smaller change from 12 to 8% O2 for 5 min evoked a similar pattern of response to that evoked by 8% O2 in NB rats, except that heart rate (HR) and CBF decreased progressively. However, 8-PT increased baseline VE and reduced ABP in 12% O2 and reduced the secondary decrease in VE and HR evoked by 8% O2, but had no effect on the fall in ABP, or change in muscle vascular conductance. 5. We propose that in CHB rats (i) there is accentuation of the components of the response to acute hypoxia (the fall in ABP, HR and CBF) that form a positive feedback loop which promotes central ventilatory depression and (ii) that adenosine exerts a tonic inhibitory influence on VE and vasodilator influence in muscle and mediates the secondary fall in VE, but not the muscle vasodilation induced by acute hypoxia.