gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Crosstalk of P2X1 and P2Y6 receptors regulates renovascular resistance in mice

Interaktion von P2X1 und P2Y6 Rezeptoren reguliert den renovaskulären Widerstand in Mäusen

Meeting Abstract (Hypertonie 2004)

  • presenting/speaker O. Vonend - Medizinische Klinik I, Marienhospital Herne (Herne, D)
  • S. Habbel - Medizinische Klinik I, Marienhospital Herne (Herne, D)
  • J. Stegbauer - Medizinische Klinik I, Marienhospital Herne (Herne, D)
  • B. Robaye - Institut de Recherche Interdisciplinaire (Bruxelles, B)
  • J.-M. Boeynaems - Institut de Recherche Interdisciplinaire (Bruxelles, B)
  • L.C. Rump - Mediziinische Klinik I, Marienhospital Herne (Herne, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP42

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch042.shtml

Veröffentlicht: 10. August 2005

© 2005 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 vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Aim of the study was to investigate whether ATP, released as a sympathetic neurotransmitter, modulates renovascular resistance in mice. Furthermore, P2Y and P2X receptor agonists and antagonists were tested on wildtype and P2Y4 receptor knockout mice to evaluate which receptor-subtypes are responsible for renal vasoconstriction induced by neuronal and non-neuronal released ATP.

Mice were anaesthesized and renal arteries were cannulated through the abdominal aorta. The kidneys were isolated and perfused with Krebs-Henseleit solution. Electrodes were placed around the renal arteries to stimulate the renal nerves electrically. The perfusion pressure was monitored continuously.

Renal nerve stimulation with 1, 2, 5, 7.5, and 10 Hz induced renal vasoconstriction in a frequency dependent manner in wildtype and P2Y4 KO mice. Pressure responses to low frequency stimulation (1, 2 Hz) were resistant to blockade by the non-selective alpha-adrenoceptor antagonist phentolamine (1µM) but abolished by the selective P2X1/3-receptor antagonist NF279 (10µM). In wildtype animals ATP, the selective P2X1/3 receptor agonist alpha,beta-mATP and the P2Y2/4/6 receptor agonist UTP induced renal vasoconstriction with the following rank order of potency: alpha,beta-mATP>ATP=UTP=UDP. Only alpha,beta-mATP was inhibited significantly by NF279. Although α,β-mATP desensitizes the P2X1/3 receptor it enhances the UTP mediated renal vasoconstriction. Dose concentration response curves of UTP were not significantly different in wildtype and P2Y4 receptor KO mice.

These data demonstrate that ATP at physiological firing rates is the predominant sympathetic vasoconstrictive neurotransmitter and mediates its function by activation of P2X1receptors. Vasoconstriction of renal vessels induced by paracrine released UTP and UDP also demonstrates involvement of P2Y6 receptors. In addition, desensitization of P2X1 receptors by alpha,beta-mATP potentiates P2Y6 receptor mediated renal vasoconstriction.