DISPARATE EFFECTS OF ADENOSINE-A(1)-RECEPTOR AND A(2)-RECEPTOR AGONISTS ON INTRARENAL BLOOD-FLOW

Endogenous adenosine, secreted locally by the kidney during tissue hyp oxia, induces heterogeneous renal hemodynamic responses. We investigat ed 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 interstiti um 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 mumol) lowered cortical blood flow to 27 +/- 10% of baseline (n = 7, P < 0.0005). Medullary blood flow response was biphas ic, i.e., a transient decrease in flow to 52 +/- 8% of baseline (n = 1 7, P < 0.0001) followed by a more-sustained increase in flow to 135 +/ - 6% (n = 17, P < 0.0001). N6-cyclopentyladenosine, an adenosine recep tor 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 basel ine, respectively. By contrast, hyl)phenethylamino]-5'-N-ethylcarboxam idoadenosine (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 predominantl y increases medullary flow via A1 and A2 receptors, respectively. Thes e hemodynamic responses could play a role in protection of the outer m edulla from hypoxia.