Dipyridamole decreases glomerular filtration in the sodium-depleted dog. Evidence for mediation by intrarenal adenosine.
To determine the renal effects of inhibiting the uptake and subsequent metabolism of endogenous adenosine, dipyridamole, a nucleoside transport inhibitor, was infused intrarenally into anesthetized dogs. Dipyridamole (24 micrograms/kg per min) inhibited the cellular extraction of [14C]adenosine (72 +/- 3% vs. 9 +/- 3%) and elevated the excretion of endogenous adenosine (0.60 +/- 0.08 to 1.70 +/- 0.21 nmol/min, P less than 0.05). The action of exogenous adenosine to decrease glomerular filtration rate is known to be enhanced by sodium depletion, and is minimal or absent in sodium-loaded animals. To ascertain whether dietary sodium intake alters the renal effects of elevated endogenous adenosine, dipyridamole was infused into sodium-depleted and sodium-loaded dogs. In the sodium-depleted dogs (n = 9), dipyridamole infusion decreased the glomerular filtration rate by 59 +/- 7% (20 +/- 1 to 8 +/- 2 ml/min, P less than 0.05) which returned to control levels within 30 minutes after stopping infusion of dipyridamole. Renal vascular resistance was unchanged during dipyridamole infusion. In the sodium-loaded dogs (n = 5), dipyridamole had no effect on glomerular filtration rate (22 +/- 4 vs. 25 +/- 3 ml/min) or renal vascular resistance. In a separate series of sodium-depleted dogs (n = 8), the dipyridamole-induced decrease in glomerular filtration rate was completely reversed or inhibited by theophylline, an adenosine receptor antagonist. These experiments demonstrate that inhibition of cellular uptake of adenosine elevates adenosine levels, that dipyridamole decreases glomerular filtration rate in sodium-depleted but not sodium-loaded dogs, and that the decrease in glomerular filtration rate is inhibited by theophylline. We conclude that the decrease in glomerular filtration rate during dipyridamole administration is mediated by increased endogenous adenosine.
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D004176:Dipyridamole / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011865:Radioisotope Dilution Technique; D012964:Sodium / Q000008:administration & dosage / Q000172:deficiency*; D013806:Theophylline / Q000494:pharmacology
D004176:Dipyridamole; D012964:Sodium; D013806:Theophylline; D000241:Adenosine