The roles of adenosine in regulating the respiratory and cardiovascular systems in chronically hypoxic, adult rats.

1. We have investigated the roles of adenosine in regulating the respiratory and cardiovascular systems of rats that were made chronically hypoxic for 3-4 weeks from 6 weeks of age (CH rats) in an hypoxic chamber at 12% O2. They were studied under anaesthesia while breathing 12% O2 and during acute hypoxia (breathing 8% O2 for 5 min) before and after addition of the adenosine receptor antagonist 8-phenyltheophylline (8-PT, 10 mg kg-1). The results were compared with those obtained from normoxic (N) rats in a previous study. 2. CH rats breathing 12% O2 had greater minute ventilation (VP) than N rats breathing air, but their levels of arterial blood pressure (ABP), heart rate (HR), femoral vascular conductance (FVC) and cerebral vascular conductance (CVC) were fully comparable. 8-PT increased tidal volume (VT) in CH rats indicating a greater tonic central inhibitory influence of adenosine on VT than in N rats. However, 8-PT had no effect on cardiovascular variables, indicating no tonic cardioinhibitory or vasodilator influence of adenosine in CH rats. 3. Acute hypoxia in CH rats increased VE such that at the 5th minute of 8% O2 absolute VE was comparable to that of N rats breathing 8% O2. Moreover, in CH rats 8-PT increased VT at the 5th minute of 8% O2 indicating that the central inhibitory influence of adenosine limits the ability to maintain VT in acute hypoxia as it does in N rats. 4. Eight per cent O2 also produced a full in ABP in CH rats that was comparable to that induced in N rats by the larger change from air to 8% O2. However, the changes in HR were similar in CH and N rats while the increases in FVC and CVC were smaller in CH rats. This suggests that the ability of the secondary effects of hyperventilation and of the baroreceptor reflex to maintain cardiac output and thereby ABP is reduced in CH rats. 5. Whereas 8-PT substantially reduced the hypoxia-induced increases in FVC and CVC in N rats, it had a small effect in CH rats (P = 0.054 and 0.06, respectively). Further, acute hypoxia in CH rats had no effect on the K+ concentration in the venous efflux of hindlimb K+ (KV+) before or after 8-PT treatment. We suggest that in CH rats, the dilator influence of adenosine in acute hypoxia occurs via actions on the blood vessel walls: there was no evidence that adenosine can release dilator concentrations of K+ from skeletal muscle fibres in CH rats as proposed for N rats.