Oxygen delivery and oxygen consumption in rat hindlimb during systemic hypoxia: role of adenosine

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Abstract
1. In anaesthetised rats, the increase in femoral vascular conductance (FVC) evoked by moderate systemic hypoxia is mediated by adenosine acting on A(1) receptors. It is also nitric oxide (NO) dependent: it is attenuated by NO synthase (NOS) inhibition, but restored when baseline FVC is restored by sodium nitroprusside (SNP), a NO donor. However, under these conditions there was in increase in the critical O(2) delivery (D(O2,crit)) at which hindlimb O(2) consumption (V(O2)) becomes directly dependent upon O(2) delivery (D(O2)), indicating that V(O2) is regulated by newly synthesised NO. 2. In the present study, after NOS inhibition, when baseline FVC was restored with SNP infusion, the increases in FVC evoked by breathing 12 and 8 % O(2) were reduced by the A(1) receptor antagonist DPCPX, by 60 and 40 %, respectively (n = 8). The A(2A) receptor antagonist ZM241385 reduced the FVC increase evoked by 12 % O(2) (by 45 %, n = 8), but did not alter that evoked by 8 % O(2). 3. DPCPX also reduced the increases in FVC evoked by graded systemic hypoxia, breathing 14-6 % O(2) and increased D(O2,crit), from 0.64 +/- 0.06 to 0.95 +/- 0.07 ml O(2) min(-1) kg(-1) (control vs. DPCPX). However, ZM241385 (n = 8) had no effect on the FVC increases or on D(O2,crit) (0.70 +/- 0.02 ml O(2) min(-1) kg(-1), n = 8). 4. Thus, the increases in FVC evoked by mild to severe systemic hypoxia are mediated by A(1) receptors. These responses, which are attributable to proximal arteriolar dilatation, help maintain D(O2). Even after NOS inhibition, adenosine still increases FVC via A(2A) (moderate hypoxia only) and A(1) receptors, providing baseline levels of NO are present. Furthermore, adenosine, acting via A(1) receptors, is important in determining D(O2,crit) and therefore in maintaining V(O2). We propose that this is achieved by A(1)-evoked dilatation of terminal arterioles and is mediated by increased synthesis of NO.

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