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

Abstract

1. In rats housed in a hypoxic chamber at 12% 02 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 02 concentration in the inspirate. Both CH and N rats were anaesthetized with Saffan. They had haematocrits of 550 + 0 9% (mean + S.E.M.) and 41P9 + 05%, respectively.2. In CH rats breathing 12% 02 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 + 1P2 and 11.5 + 06% in all venules in CH and N rats, respectively. 3. In CH rats, the change from 12% 02 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% 02 for 3 min induced net dilatation (3 9 + 1 8 % in arterioles and 4-7 + 0O8% 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% 02 in N rats (to -2f4 + 1f3% in arterioles and 2f0 + 0 9% in venules). 4. In CH rats, the change from 12 to 8 02 produced net dilatation as great as that induced in N rats by the larger change from air to 8% 02: 8-5 + 2-6 and 5 0 + 3 7% in arterioles and 103 + 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 % 02 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% 02 despite its contribution to the dilatation induced in N rats by acute exposure to 12% 02. This may reflect the greater haematocrit in CH rats which normalized the 02 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.

Chemoreceptors and cardiovascular control in acute and chronic systemic hypoxia

“…We found that the changes in arteriolar diameter induced when CH rats were switched from breathing 12% O 2 to 8% O 2 were just as great as those induced in N rats when they were switched from breathing air to 8% O 2 (106). Further, the effects of adenosine receptor blockade on these responses were fully comparable in the CH and N rats: in each section of the arteriolar tree, mean increases in diameter were reduced or reversed to mean decreases in diameter and quantitatively the sizes of these effects were similar in CH and N rats (106).…”

“…We found that the changes in arteriolar diameter induced when CH rats were switched from breathing 12% O 2 to 8% O 2 were just as great as those induced in N rats when they were switched from breathing air to 8% O 2 (106). Further, the effects of adenosine receptor blockade on these responses were fully comparable in the CH and N rats: in each section of the arteriolar tree, mean increases in diameter were reduced or reversed to mean decreases in diameter and quantitatively the sizes of these effects were similar in CH and N rats (106). The maximal dilatation produced by topical application of adenosine in each section of the arteriolar tree was also similar in the CH and N rats, so there was no reason to suppose that the arterioles of the CH rats were capable of greater maximal dilatation in response to adenosine or any other dilator influence than those of N rats (106).…”

“…Further, the effects of adenosine receptor blockade on these responses were fully comparable in the CH and N rats: in each section of the arteriolar tree, mean increases in diameter were reduced or reversed to mean decreases in diameter and quantitatively the sizes of these effects were similar in CH and N rats (106). The maximal dilatation produced by topical application of adenosine in each section of the arteriolar tree was also similar in the CH and N rats, so there was no reason to suppose that the arterioles of the CH rats were capable of greater maximal dilatation in response to adenosine or any other dilator influence than those of N rats (106). We have made very similar observations in the microcirculation of the intestinal mesentery in CH and N rats (107).…”

The effects of acute and chronic systemic hypoxia on muscle oxygen supply and oxygen consumption in the rat

“…Accordingly, our direct observations on the spinotrapezius muscle of CH rats breathing 12 YO 0, revealed that acute exposure to air-breathing induced constriction in all arterioles. On the other hand, the challenge of acute systemic hypoxia ( 8 % 0,) induced dilatation in the majority of arterioles and constriction in the others as in N rats (see above), but the arterioles of CH rats seemed more sensitive to the dilator influences of acute hypoxia and to adenosine than those of N rats (Mian & Marshall, 1996). This raised the possibility that the feedback control of 0, distribution within skeletal muscle becomes more efficient in chronic systemic hypoxia.…”

“…The experiments were performed on CH rats that had been kept in a normobaric hypoxic chamber at 1 2 % 0, for 3-4 weeks and on N rats that had been reared in air (see Mian & Marshall, 1996;Thomas & Marshall, 1997). We monitored 0, delivery t o hindlimb muscles and muscle Pop in N rats when they were breathing air or were acutely switched to breathing I2 or 8 %I 0, and in CH rats when they were breathing 12 YO 0,, or were acutely switched to air-breathing, or t o 8 YO 0,.…”