Artikel
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
Suche in Medline nach
Autoren
Veröffentlicht: | 11. November 2004 |
---|
Gliederung
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.