Diadenosine pentaphosphate modulates glomerular arteriolar tone and glomerular filtration rate.
BACKGROUND
Mechanisms and participating substances involved in the reduction of glomerular filtration (GFR) in contrast-induced acute kidney injury (CI-AKI) are still matter of debate. We hypothesized that diadenosine polyphosphates are released by the action of contrast media on tubular cells and may act on glomerular arterioles and reduce GFR.


METHODS
Freshly isolated rat tubules were treated with the contrast medium iodixanol (47 mg iodine per mL) at 37 °C for 20 min. The content of Apn A (n = 3-6) in the supernatant of treated tubules and in the plasma of healthy persons and patients with AKI was analysed using reversed-phase chromatography, affinity chromatography and mass spectrometry. GFR was obtained in conscious mice by inulin clearance. Concentration response curves for Apn A (n = 3-6, 10(-12) -10(-5)  mol L(-1) ) were measured in isolated perfused glomerular arterioles.


RESULTS
Iodixanol treatment of tubules significantly increased the concentration of Apn A (n = 3-5) in the supernatant. Ap6 A was below the detection limit. AKI patient shows higher concentrations of Apn A compared to healthy. Application of Ap5 A significantly reduced the GFR in conscious mice. Ap5 A reduced afferent arteriolar diameters, but did not influence efferent arterioles. The constrictor effect on afferent arterioles was strong immediately after application, but weakened with time. Then, non-selective P2 inhibitor suramin blocked the Ap5 A-induced constriction.


CONCLUSIONS
The data suggest that Ap5 A plays a role in the pathophysiology of CI-AKI. We show a contrast media-induced release of Ap5 A from tubules, which might increase afferent arteriolar resistance and reduce the GFR.
Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
A
A
Patzak
M
M
Carlström
M M
MM
Sendeski
E Y
EY
Lai
Z Z
ZZ
Liu
J
J
Sällström
J
J
Flöge
B
B
Heintz
J
J
Jankowski
V
V
Jankowski
D058186:Acute Kidney Injury / Q000188:drug therapy; D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008810:Mice, Inbred C57BL; D017207:Rats, Sprague-Dawley; D014283:Triiodobenzoic Acids
D015226:Dinucleoside Phosphates; D014283:Triiodobenzoic Acids; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C044834:iodixanol
afferent arteriole; contrast-induced acute kidney injury; diadenosine polyphosphates; glomerular filtration rate; human; mouse