The
adenosine A1 receptor antagonist (
FR113453) prevents
glycerol- but not
mercury-induced
acute renal failure. To clarify this mechanism,
adenosine concentration in the renal vein was measured serially. Plasma
adenosine in the renal vein increased from the preinjection value of 120.6 +/- 15.4 (mean +/- SEM) pmol/ml to 426.9 +/- 107.5, 407.0 +/- 70.1 and 283.9 +/- 22.9 pmol/ml at 1, 5 and 60 min after
intramuscular injection of 10 mg/kg of 50%
glycerol into Sprague-Dawley rats. On the other hand, intramuscular vehicle (
0.9% NaCl) injection and subcutaneous administration of 10 mg/kg of
HgCl2 did not change or caused mild elevation of
adenosine concentration in the renal vein. Furthermore, simultaneous blood collection from the carotid artery, renal vein and inferior vena cava revealed a greater increase in
adenosine concentration in the inferior vena cava than in the artery or renal vein. These findings were not affected by the administration of
FR113453 or vehicle (
methylcellulose). The increase in
adenosine in the inferior vena cava was derived from the release from the acutely damaged muscles due to
glycerol injection. These findings suggest that the effect of
adenosine A1 antagonist to prevent
glycerol-induced
acute renal failure is due to the inhibition of
adenosine A1 receptor in the kidneys during the release of
adenosine through the inferior vena cava. Therefore, the release of
adenosine from the muscle and
hemolysis plays an important role to induce
acute renal failure in the
glycerol-injected rat.