Role of 5'-nucleotidase in adenosine-mediated renal vasoconstriction during hypoxia.
Regulation of renal function by endogenous adenosine production was examined in isolated perfused rat kidneys. Reducing perfusate pO2 from 400 +/- 15 to 130 +/- 5 mm Hg for 20 min created an energy deficit and increased adenosine in venous perfusate (0.06 +/- 0.02 to 0.79 +/- 0.15 microM) and snap-frozen renal cortex (5.6 +/- 1.4 to 16.7 +/- 2.7 nmol/g wet wt.). A competitive inhibitor of 5'-nucleotidase, alpha,beta-methyleneadenosine diphosphate (120 microM), inhibited the production of adenosine during hypoxia (perfusate, 0.26 +/- 0.05 microM and renal cortex, 3.1 nmol/g) but did not prevent the decline in cortical tissue ATP and ADP. The inhibitor was concentrated 3-fold in renal cortex compared to perfusate and could therefore inhibit both ecto and endo 5' nucleotidases. Vascular resistance increased 11.1 +/- 0.5% during hypoxia. Inhibition of 5'-nucleotidase reduced the vasoconstrictive response by 40% (P less than .01). An A1 antagonist, 1,3-diprophyl-8-(2-amino-4-chlorophenyl)xanthine (10(-5) M), reduced the effect of hypoxia on vascular resistance by 60% (P less than .005). Adenosine deaminase (7-14 U/ml) added during hypoxia reduced venous adenosine from 1.0 to 0.3 microM and reduced vascular resistance by 3 +/- 1%. Neither the inhibitors nor adenosine deaminase significantly altered the response of glomerular filtration rate or sodium reabsorption to hypoxia. These results indicate that either ecto or endo 5'-nucleotidase controls the renal production of adenosine during an energy deficit and that endogenous adenosine constricts the renal vasculature.
D015720:5'-Nucleotidase; D000227:Adenine Nucleotides / Q000032:analysis; D000241:Adenosine / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D009708:Nucleotidases / Q000502:physiology*; D010100:Oxygen / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology
D000227:Adenine Nucleotides; D014970:Xanthines; D009708:Nucleotidases; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase; C046379:1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine; D000241:Adenosine; D010100:Oxygen