gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Impaired expression of endothelial KCa-channels and EDHF-mediated vasodilations in experimental CRF

Vermindert Expression endothelialer KCa-Kanäle und EDHF-mediierter Vasodilatation bei experimenteller chronischer Niereninsuffizienz

Meeting Abstract (Hypertonie 2003)

  • presenting/speaker I. Eichler - Charite Campus Benjamin Franklin (Berlin, D)
  • H. Schönfelder - Charite Campus Benjamin Franklin (Berlin, D)
  • S. Brakemeier - Charite Campus Benjamin Franklin (Berlin, D)
  • A. Knorr - Charite Campus Benjamin Franklin (Berlin, D)
  • I. Grgic - Charite Campus Benjamin Franklin (Berlin, D)
  • R. Köhler - Charite Campus Benjamin Franklin (Berlin, D)
  • J. Hoyer - Charite Campus Benjamin Franklin (Berlin, D)

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochV34

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2003/03hoch034.shtml

Published: November 11, 2004

© 2004 Eichler et al.
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Outline

Text

Background

Chronic renal failure (CRF) is associated with increased cardiovascular morbidity, abnormal arterial tone, and endothelial dysfunction. Small and intermediate-conductance Ca2+-activated K+-channels (KCa) are important regulators of endothelial function by mediating endothelial hyperpolarization which is prerequisite for endothelium-derived hyperpolarizing factor (EDHF)-meditated vasodilations. In the present study we tested the hypothesis whether an altered function of endothelial KCa and diminished EDHF-meditated vasodilation contribute to endothelial dysfunction in experimental CRF.

Methods

Endothelial KCa-currents and endothelium-dependent vasodilations in rat carotid arteries (CA) from SD rats were assessed by use of the patch-clamp technique and a pressure-myograph 8 weeks after either subtotal 5/6 nephrectomy (n=6) or sham operation (n=5).

Results

In isolated EC, KCa-currents induced by cell dialysis with Ca2+ were significantly reduced in nephrectomized rats (18 pA ± 2 SE at Vhold of 0 mV, n=42) compared to sham-operated controls (40 pA ± 6 SE; P<0.0001, n=29). In phenylephrine-preconstricted CA, acetylcholine (ACh)-induced NO and prostacyclin-independent vasodilations were present in sham-operated rats (10 ± 1 % at 1 mM ACh), but almost absent in 5/6 Nx rats (2 ± 2%, P<0.05). 1-EBIO (100 mM), a selective opener of endothelial small and intermediate KCa induced vasodilation of 15 ± 4% in sham-operated rats, but was ineffective in 5/6 Nx-rats. In experiments without blocking NO and prostacyclin synthesis, endothelium-dependent vasodilation to ACh was significantly reduced by ~15 % in 5/6 Nx-rats.

Conclusions

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