gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Impaired EDHF-mediated vasodilatation and K+ channel function in chronic renal failure

Defekte EDHF-vermittelte Vasodilatation und K+-Kanalfunktion bei chronischer Niereninsuffizienz

Meeting Abstract (Hypertonie 2004)

  • R. Koehler - Campus Benjamin Franklin, Berlin, D
  • I. Eichler - Campus Benjamin Franklin, Berlin, D
  • H. Schönfelder - Campus Benjamin Franklin, Berlin, D
  • P. Heinau - Campus Benjamin Franklin, Berlin, D
  • H. Si - Campus Benjamin Franklin, Berlin, D
  • J. Hoyer - Campus Benjamin Franklin, Berlin, D

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP11

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

Published: August 10, 2005

© 2005 Koehler 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.



Background: Chronic renal failure is associated with increased cardiovascular morbidity, abnormal arterial tone, and endothelial dysfunction. Ca2+-activated K+-channels (KCa) are important regulators of endothelial function by controlling endothelial hyperpolarization and thus endothelium-derived hyperpolarizing factor (EDHF)-meditated vasodilations. Here we tested the hypothesis whether an altered function of endothelial KCa and diminished EDHF-meditated vasodilatation contribute to endothelial dysfunction in experimental chronic renal failure (CRF).

Methods: Functional expression of endothelial KCa currents and endothelium-dependent vasodilatations in rat carotid arteries (CA) were assessed by using patch-clamp techniques, single-cell-RT-PCR, and a pressure-myograph, 8 weeks after either subtotal 5/6 nephrectomy in normotensive (5/6NxN) and hypertensive (5/6NxH) or sham-operated (Sham) rats.

Results: Acetylcholine (ACh)-induced EDHF-mediated vasodila-tations were present in Sham, but almost absent in both 5/6NxN and 5/6NxH. 1-EBIO, a selective opener of endothelial small and intermediate KCa induced a substantial vasodilatation in Sham, but induced very small vasodilatation in 5/6NxH and in 5/6NxN. In experiments without blocking NO/prostacyclin synthesis, endothelium-dependent vasodilatation to ACh was significantly reduced in both 5/6NxN and 5/6NxH. In patch-clamp experiments, mean KCa currents were significantly reduced in ECs from 5/6NxH and 5/6NxN when compared to Sham. In 5/6Nx rats compared to Sham, single-cell-RT-PCR analysis revealed a greatly reduced frequency of ECs expressing the KCa genes SKCa3 and IKCa1.

Conclusions: Experimental CRF leads to a loss of EDHF-type vasodilatation which was caused at least in part by an impaired functional expression of endothelial hyperpolarizing KCa. The loss of EDHF-type vasodilatation may contribute to endothelial dysfunction and abnormal arterial tone in CRF.