Diadenosine pentaphosphate modulates glomerular arteriolar tone and glomerular filtration rate. (3rd December 2014)

• Record Type: Journal Article
• Authors: Patzak, A.; Carlström, M.; Sendeski, M. M.; Lai, E. Y.; Liu, Z. Z.; Sällström, J.; Flöge, J.; Heintz, B.; Jankowski, J.; Jankowski, V.
• Is Part Of: Acta physiologica. Volume 213:Number 1(2015:Jan.)
• Page Start: 285
• Page End: 293
• Publication Date: 2014-12-03
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12425
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" id="apha12425-abs-0001"> <title>Abstract</title> <sec id="apha12425-sec-0001" sec-type="section"> <title>Introduction</title> <p>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.</p> </sec> <sec id="apha12425-sec-0002" sec-type="section"> <title>Methods</title> <p>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 Ap<sub>n</sub>A (<italic>n </italic>= 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 Ap<sub>n</sub>A (<italic>n </italic>= 3–6, 10<sup>−12</sup>–10<sup>−5</sup> mol L<sup>−1</sup>) were measured in isolated perfused glomerular arterioles.</p> </sec> <sec id="apha12425-sec-0003" sec-type="section"> <title>Results</title> <p>Iodixanol treatment of tubules significantly increased the concentration of Ap<sub>n</sub>A (<italic>n </italic>= 3–5) in the supernatant. Ap<sub>6</sub>A was below the detection limit. AKI patient shows higher concentrations of Ap<sub>n</sub>A compared to healthy. Application of Ap<sub>5</sub>A significantly reduced the GFR in conscious mice. Ap<sub>5</sub>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 Ap<sub>5</sub>A‐induced constriction.</p> </sec> <sec id="apha12425-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The data suggest that Ap<sub>5</sub>A plays a role in the pathophysiology of CI‐AKI. We show a contrast media‐induced release of Ap<sub>5</sub>A from tubules, which might increase afferent arteriolar resistance and reduce the GFR.</p> </sec> </abstract>