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 respi ratory and cardiovascular systems of rats that were made chronically h ypoxic for 3-4 weeks from 6 weeks of age (CH rats) in an hypoxic chamb er at 12% O-2. They were studied under anaesthesia while breathing 12% O-2 and during acute hypoxia (breathing 8% O-2 for 5 min) before and after addition of the adenosine receptor antagonist 8-phenyltheophylli ne (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% O-2 had greater minute ventilation (V-E) than N rats breathing air, bu t their levels of arterial blood pressure (ABP), heart rate (HR), femo ral vascular conductance (FVC) and cerebral vascular conductance (CVC) were fully comparable, 8-PT increased tidal volume (V-T) in CH rats i ndicating a greater tonic central inhibitory influence of adenosine on V-T than in N rats. However, 8-PT had no effect on cardiovascular var iables, indicating no tonic cardioinhibitory or vasodilator influence of adenosine in CH rats. 3. Acute hypoxia in CH rats increased V-E suc h that at the 5th minute of 8% O-2 absolute V-E was comparable to that of N rats breathing 8% O-2. Moreover, in CH rats 8-PT increased V-T a t the 5th minute of 8% O-2 indicating that the central inhibitory infl uence of adenosine limits the ability to maintain V-T in acute hypoxia as it does in N rats. 4. Eight per cent O-2 also produced a fall in A BP ih CH rats that was comparable to that induced in N rats by the lar ger change from air to 8% O-2. However, the changes in HR were similar in CH and N rats while the increases in FVC and CVC were smaller in C H rats. This suggests that the ability of the secondary effects of hyp erventilation and of the baroreceptor reflex to maintain cardiac outpu t 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 ha d a small effect in CH rats (P = 0.054 and 0.06, respectively). Furthe r, acute hypoxia in CH rats had no effect on the K+ concentration in t he venous efflux of hindlimb K+ (K-v(+)) before or after 8-PT treatmen t. We suggest that in CH rats, the dilator influence of adenosine in a cute hypoxia occurs via actions on the blood vessel walls: there was n o evidence that adenosine can release dilator concentrations of K+ fro m skeletal muscle fibres in CH rats as proposed for N rats.