gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

P2Y2 and P2X7 receptors in a model of chronic renal failure

P2Y2- und P2X7-Rezeptor Expression am Modell der chronischen Niereninsuffizienz

Meeting Abstract (Hypertonie 2003)

Suche in Medline nach

  • presenting/speaker O. Vonend - Bochum, D
  • S. Potthoff - Bochum, D
  • J. Stegbauer - Bochum, D
  • L. Rump - Bochum, D

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochV33

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2003/03hoch033.shtml

Veröffentlicht: 11. November 2004

© 2004 Vonend et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Chronic renal failure is often associated with sympathetic overactivity and severe hypertension. Renal sympathetic nerve endings release transmitters such as Norepinephrine, Neuropeptide Y and ATP. In-vitro studies revealed that these transmitters, in particular ATP, induce vasoconstriction but moreover modulate renal cell proliferation. In vivo these mitogenic effects appears to be a basis for progression of sympathetic overactivity, leading to high blood pressure and organ damage. While the ATP receptor P2Y2 mediates cell proliferation, P2X7 receptors modulate cell death.

To examine the significance of these receptors in experimental chronic renal failure, we analyzed P2Y2 and P2X7 receptor expression in subtotally nephrectomized mice.

Ten days after subtotal nephrectomies, performed on adult FVB-mice, remnant kidneys were removed for further investigations. Serum-BUN ten days after operation increased from 85.0±9.5 to 186.7±10.2 mg/dl (n=4). Some animals received 250µl BrdU (10mM) i.p. 20h prior termination to estimate DNA-synthesis. Immunocytochemitry with AntiBrdU revealed increased proliferation in kidneys of subtotally nephrectomized mice. P2Y2 and P2X7 receptors were localized by immunocytochemistry primarily in glomeruli. P2X7 receptor expression could be detected in blood vessels and in peritubular structures, somewhat more pronounced in tissue of subtotally nephrectomized mice. To quantify expression of P2Y2 and P2X7 receptors, real-time RT-PCR was performed. mRNA expression, normalized to GAPDH, was increased 3,4±1,1 and 14,8±4,2 fold (n=4) for P2Y2 and P2X7 -receptors compared to sham operated animals. mRNA levels for TGF-ß and apoptosis related Bax increased 3.3±1.6 and 6.1± 3.2 fold (n=4). Long term experiments with P2 receptor blockers have to demonstrate to what extend P2Y2 and P2X7 receptor expression is supporting or hindering adaptive mechanisms in chronic renal failure leading to sympathetic overactivity and hypertension.