Disparate effects of adenosine A₁- and A₂-receptor agonists on intrarenal blood flow

Endogenous adenosine, secreted locally by the kidney during tissue hypoxia, induces heterogeneous renal hemodynamic responses. We investigated the cortical and outer medullary blood flow responses to intrarenal infusions of adenosine and adenosine A₁- and A₂-receptor agonists in anesthetized rats. These agents were infused into the renal interstitium through chronically implanted capsules, and blood flow was measured by laser Doppler probes. Short (1 min, 0.05 ml) intrarenal infusions of adenosine (0.5 μmol) lowered cortical blood flow to 27 ± 10% of baseline (n = 7, P < 0.0005). Medullary blood flow response was biphasic, i.e., a transient decrease in flow to 52 ± 8% of baseline (n = 17, P < 0.0001) followed by a more- sustained increase in flow to 135 ± 6% (n = 17, P < 0.0001). N⁶- cyclopentyladenosine, an adenosine receptor A₁ agonist, reduced both cortical and medullary blood flow to 59 ± 4% (n = 10, P < 0.0001) and 38 ± 5% (n = 11, P < 0.0001) of baseline, respectively. By contrast, 2-[p- (carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS-21680C), an adenosine receptor A₂ agonist, increased dramatically the medullary blood flow to 184 ± 15% of baseline (n = 12, P < 0.0005), without major changes in cortical flow. We conclude that intrarenal adenosine reduces cortical blood flow and predominantly increases medullary flow via A₁ and A₂ receptors, respectively. These hemodynamic responses could play a role in protection of the outer medulla from hypoxia.