gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

The kappa 2A-Adrenoceptor modulates the Noradrenaline- and ATP-Release in Isolated Perfused Kidneys of Wildtype- and kappa 2A -Adrenoceptor Knockout Mice

Der kappa 2A-Adrenozeptor reguliert die Noradrenalin und ATP Freisetzung in isoliert perfundierten Nieren von Wildtype und kappa 2A –Adrenozeptor Knockout Mäusen

Meeting Abstract

  • S. Habbel - Zentrum für klinische Forschung, Bochum (Bochum, D)
  • J. Stegbauer - Zentrum für klinische Forschung, Bochum (Bochum, D)
  • O. Vonend - Zentrum für klinische Forschung, Bochum (Bochum, D)
  • L. Hein - Universität Würzburg (Würzburg, D)
  • L.C. Rump - Marienhospital, Herne

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP170

The electronic version of this article is the complete one and can be found online at:

Published: August 8, 2006

© 2006 Habbel et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Sympathetic overactivity and increased nordrenaline (NA) spillover are closely associated with progresiv renal failure. The present study investigates whether the a2A-adrenoceptor-subtype represents the presynaptic adrenoceptor that is activated by neuronally released noradrenaline (NA) in mouse kidney.

This is of particular interest, since presynaptic adrenoceptors are supposed to modulate, in addition to NA, the release of the cotransmitter ATP. Moreover, we tested whether the sympathetic cotransmitter ATP modulates NA release by activating putative presynaptic P2 receptors.

Wildtype and a2A-adrenoceptor-KO mice were anaesthetized and renal arteries were cannulated through the abdominal aorta. The kidneys were then perfused with Krebs-Henseleit solution at a constant rate (7.25 ml / min / g). Electrodes were placed around the renal arteries to stimulate the renal nerves. The perfusion solution was collected and, endogenously released NA was measured by HPLC. The perfusion pressor was monitored continuously.

Renal nerve stimulation (RNS) induced a frequenzy (1, 2, 5, 7.5, 10, 15 Hz) dependant release of NA (1156+/-223, 2509+/-332, 6728+/-584, 11542+/-1167, 19094+/-1241, 23846+/-2388 pg NA / g kidney +/- SE). In a2A-adrenoceptor-KO mice RNS at 5 Hz increased NA release 2.7 fold. In wildtype animals the non selective a-adrenoceptor blocker phentolamine increased RNS induced NA-release in a concentration dependent manner up to 350% of control. No facilitation by phentolamine was observed in a2A-adrenoceptor KO. In control experiments without phentolamine no significant differences in NA-release were observed.

Phentolamine decreased the RNS induced pressor responses in WT mice at higher frequencies. NA does not seem to be responsible for pressor responses at lower frequencies.

Pressor reponses to 1 Hz and 2 Hz cannot be blocked by prazosin. Inhibition of presynaptic a-receptors increases purinergic pressor responses up to 300% in WT but not in a2A KO mice.

ATP induced NA release idependant of RNS.

We established an invitro mouse model to analyse real sympathetic neurotransmitter release. Experiments with knockout mice demonstrated that the a2A-adrenoceptor subtype is responsible for modulating NA release in mouse kidney. Although NA only mediates pressor responses at high frequency RNS. At low frequencies ATP seems to be the predominant transmitter. ATP release as well seems to be partially mediated by presynaptic a2A receptors. In addition, there are presynpatic P2 receptors which modulate the release of large amounts of NA from sympathtic nerve endings independently of RNS.