The behaviour of muscle microcirculation in chronically hypoxic rats: the role of adenosine.

1. In rats housed in a hypoxic chamber at 12% O2 for 3-5 weeks (CH) and in normal rats housed in air (N), we directly observed responses of arterial and venous vessels of the spinotrapezius muscle to changes in O2 concentration in the inspirate. Both CH and N rats were anaesthetized with Saffan. They had haematocrits of 55.0 +/- 0.9% (mean +/- S.E.M.) and 41.9 +/- 0.5%, respectively. 2. In CH rats breathing 12% O2 and N rats breathing air, arterial and venous vessels from comparable anatomical positions in the vascular tree were of similar internal diameter. They also showed similar maximum dilator responses to topical adenosine (10(-3) M); 14.1 +/- 1.1 and 16.3 +/- 1.7% in all arterioles, 15.5 +/- 1.2 and 11.5 +/- 0.6% in all venules in CH and N rats, respectively. 3. In CH rats, the change from 12% O2 to air for 3 min induced constriction in all arterioles and venules (-12.9 +/- 1.0 and -14.3 +/- 1.7%, respectively), whereas in N rats, the change from air to 12% O2 for 3 min induced net dilatation (3.9 +/- 1.8% in arterioles and 4.7 +/- 0.8% in venules). Topical application of the adenosine receptor antagonist 8-sulphophenyltheophylline (8-SPT, 10(-3) M) had no effect on control diameters in CH or N rats, nor on constrictor responses to air in CH, but reversed or reduced dilator responses to 12% O2 in N rats (to -2.4 +/- 1.3% in arterioles and 2.0 +/- 0.9% in venules). 4. In CH rats, the change from 12 to 8% O2 produced net dilatation as great as that induced in N rats by the larger change from air to 8% O2: 8.5 +/- 2.6 and 5.0 +/- 3.7% in arterioles and 10.3 +/- 1.8 and 6.4 +/- 1.9% in venules, respectively. These responses were similarly reduced by 8-SPT to -4.3 +/- 1.9 and -5.2 +/- 2.7% in arterioles and to -6.9 +/- 2.0 and -1.5 +/- 2.0% in venules, respectively. 5. These results indicate that CH rats were acclimated to 12% O2 such that the resting tone of arterial and venous vessels of muscle was comparable to that of N rats breathing air. They also suggest that adenosine had little tonic dilator influence in CH rats breathing 12% O2 despite its contribution to the dilatation induced in N rats by acute exposure to 12% O2. This may reflect the greater haematocrit in CH rats which normalized the O2 supply to muscle. However, CH rats were more sensitive than N rats to the dilator influence of acute systemic hypoxia and this was largely mediated by adenosine.