Institut for Biomedicin

Christian Aalkjær

Impaired endothelial calcium signaling is responsible for the defective dilation of mesenteric resistance arteries from db/db mice to acetylcholine

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

We aimed at assessing the role of endothelial cell calcium for the endothelial dysfunction of mesenteric resistance arteries of db/db mice (a model of type 2 diabetes) and determine whether treatment with sulfaphenazole, improves endothelial calcium signaling and function. Pressure myography was used to study acetylcholine (ACh) -induced vasodilation. Intracellular calcium ([Ca(2+)]i) transients was measured by confocal laser scanning microscopy and smooth muscle membrane potential with sharp microelectrodes. The impaired dilation to ACh observed in mesenteric resistance arteries from db/db mice was improved by treatment of the mice with sulfaphenazole for 8 weeks. The impaired dilation to ACh was associated with decreased endothelial [Ca(2+)]i and smooth muscle hyperpolarization. Sulfaphenazole applied in vitro improved endothelial mediated dilation of arteries from db/db mice both in the absence and the presence of inhibitors of nitric oxide and cyclooxygenase. Sulfaphenazole also increased the percentage of endothelial cells with ACh induced increases of [Ca(2+)]i. The study shows that impaired endothelial [Ca(2+)]i control can explain the reduced endothelial function in arteries from diabetic mice and that sulfaphenazole treatment improves endothelial [Ca(2+)]i responses to ACh and consequently endothelium-dependent vasodilation. These observations provide mechanistic insight into endothelial dysfunction in diabetes.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Pharmacology
Vol/bind767
Sider (fra-til)17-23
Antal sider7
ISSN0014-2999
DOI
StatusUdgivet - 15 nov. 2015

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