gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Increased Norepinephrine-Release in Kidneys of alpha2A- Adrenoceptor KO-Mice

Gesteigerte Noradrenalinfreisetzung in Nieren von alpha2a-Adrenozeptor Knockoutmäusen

Meeting Abstract (Hypertonie 2004)

  • presenting/speaker O. Vonend - Department of Nephrology, Marienhospital Herne, Ruhr University Bochum (Herne, D)
  • S. Habbel - Department of Nephrology, Marienhospital Herne, Ruhr University Bochum (Herne, D)
  • J. Stegbauer - Department of Nephrology, Marienhospital Herne, Ruhr University Bochum (Herne, D)
  • L. Hein - Department of Pharmacology, University of Wuerzburg (Würzburg, D)
  • L.C. Rump - Department of Nephrology, Marienhospital Herne, Ruhr University Bochum (Herne, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP44

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

Published: August 10, 2005

© 2005 Vonend 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 noradrenaline (NA) spillover are closely associated with progressive renal failure. The present study investigates whether the alpha2A-adrenoceptor subtype represents the local alpha2A-autoreceptor that is activated by neuronally released NA in mouse kidney. Moreover, we tested whether the sympathetic cotransmitter ATP modulates NA-release by activating presynaptic P2 receptors.

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. Endogenous release of NA was measured by HPLC.

Renal nerve stimulation (RNS) induced a frequency (1, 2, 5, 7.5, 10, 15 Hz) dependent release of NA (994±373, 2355±541, 6375±950, 11626±1818, 19138±2001 pg NA / g kidney ± SE). In alpha2A-adrenoceptor knockout mice RNS at 5 Hz increased NA release 2.7 fold. In wildtype animals the non selective alpha-adrenoceptor blocker phentolamine increased RNS induced NA-release in a concentration dependent manner up to 253 ± 20 % of control. No facilitation by phentolamine was observed in alpha2A-knockout mice. However, 2MeSADP inhibited RNS induced NA release by up to 30 %. ATP induced NA-release independent of RNS.

We established an in vitro mouse model to analyze renal sympathetic neurotransmitter release. Experiments with knockout mice demonstrated that the alpha2A-adrenoceptor subtype is responsible for modulating NA release in mouse kidney. Furthermore, we found evidence for inhibitory and excitatory P2 receptors, capable to further modulate neuronal NA release in the kidney.