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 mumol) 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-ethycarboxamidoadenosine (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.
Agmon
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Department of Medicine, Hadassah University Hospital, Jerusalem, Israel.
Dinour
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Brezis
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D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D007672:Kidney Cortex / Q000098:blood supply; D007679:Kidney Medulla / Q000098:blood supply; D017078:Laser-Doppler Flowmetry; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects*
D010627:Phenethylamines; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine