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

In anaesthetised rats, the increase in femoral vascular conductance (FVC) evoked by moderate systemic hypoxia is mediated by adenosine acting on A1 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 O2 delivery (DO2,crit) at which hindlimb O2 consumption (V̇O2) becomes directly dependent upon O2 delivery (DO2), indicating that V̇O2 is regulated by newly synthesised NO.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 % O2 were reduced by the A1 receptor antagonist DPCPX, by 60 and 40 %, respectively (n = 8). The A2A receptor antagonist ZM241385 reduced the FVC increase evoked by 12 % O2 (by 45 %, n = 8), but did not alter that evoked by 8 % O2.DPCPX also reduced the increases in FVC evoked by graded systemic hypoxia, breathing 14–6 % O2 and increased DO2,crit, from 0.64 ± 0.06 to 0.95 ± 0.07 ml O2 min−1 kg−1 (control vs. DPCPX). However, ZM241385 (n = 8) had no effect on the FVC increases or on DO2,crit (0.70 ± 0.02 ml O2 min−1 kg−1, n = 8).Thus, the increases in FVC evoked by mild to severe systemic hypoxia are mediated by A1 receptors. These responses, which are attributable to proximal arteriolar dilatation, help maintain DO2. Even after NOS inhibition, adenosine still increases FVC via A2A (moderate hypoxia only) and A1 receptors, providing baseline levels of NO are present. Furthermore, adenosine, acting via A1 receptors, is important in determining DO2,crit and therefore in maintaining V̇O2. We propose that this is achieved by A1-evoked dilatation of terminal arterioles and is mediated by increased synthesis of NO