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

Dysfunction of endothelial Ca2+-activated K+-channels and impaired EDHF-mediated vasodilation in experimental chronic renal insufficiency

Gestörte EDHF-mediierte Vasodilatation und KCa-Funktionen bei experimenteller chronischer Niereninsuffizienz

Meeting Abstract

  • J. Hoyer - Philipps-Universität Marburg (Marburg, D)
  • T. Maier - Philipps-Universität Marburg (Marburg, D)
  • I. Grgic - Philipps-Universität Marburg (Marburg, D)
  • C. Busch - Philipps-Universität Marburg (Marburg, D)
  • R. Köhler - Philipps-Universität Marburg (Marburg, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP86

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

Published: August 8, 2006

© 2006 Hoyer 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 insufficiency (CRI) is associated with increased cardiovascular morbidity, hypertension, and possibly endothelial dysfunction. Endothelial Ca2+-activated K+-channels (KCa) are of crucial importance in endothelial function by inducing endothelial hyperpolarization and thus endothelium-derived hyperpolarizing factor (EDHF)-meditated vasodilations. In the present study we hypothesized that decreased function of endothelial KCa and reduced EDHF-meditated vasodilation contribute to endothelial dysfunction and in experimental CRI.

Methods: Endothelial KCa-channel expression and function were investigated by combined patch-clamp and single-cell-RT-PCR analysis in the in situ endothelium of rat carotid arteries (CA) from SD rats, 8 weeks after either subtotal 5/6 nephrectomy (5/6Nx) in TXR-treated normotensive (137 ± 8 mmHg sBP, n=5) and hypertensive (195 ± 12 mmHg sBP, n=10), or sham operated controls (Sham, n=6). Endothelium-dependent vasodilatations were determined by using a pressure-myograph.

Results: Endothelial KCa-currents (IKCa) were significantly reduced in EC from hypertensive 5/6Nx rats (mean IKCa at a membrane potenial of 0 mV: 28 pA ± 3 SE, n=51, P<0.01) as well as in normotensive 5/6Nx rats (mean IKCa 23 pA ± 2 SE, n=20, P<0.001) when compared to Sham (50 pA ± 5 SE; n=39). Expression of the endothelial KCa genes IKCa1 and SKCa3 was significantly reduced in 5/6Nx rats than in Sham. Acetylcholine (ACh)-induced EDHF-mediated vasodilations were almost absent in both hypertensive (5 ± 1%, P<0.01) and normotensive 5/6 Nx rats (4 ± 4%, P<0.05) and were normal in Sham (22 ± 6 %). Selective opening of IKCa1 and SKCa3 by 1-EBIO induced vasodilation of 25 ± 6% in Sham but was readily ineffective in hypertensive (5 ± 1%) and normotensive 5/6 Nx-rats (9 ± 1%).

Conclusions: Experimental chronic renal insufficiency alone or combined with hypertension results in a loss of EDHF-mediated vasodilation. This defect appeared to be caused at least in part by an impaired expression of endothelial KCa. The loss of EDHF-type vasodilation may contribute to endothelial dysfunction and abnormal arterial tone in CRI