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Am J Physiol Heart Circ Physiol (June 12, 2003). doi:10.1152/ajpheart.00376.2003
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Submitted on April 22, 2003
Accepted on June 11, 2003

Role of Endothelial Intermediate Conductance KCa Channels in Cerebral EDHF-Mediated Dilations

Sean P Marrelli1*, Maxim S Eckmann1, and Michael S Hunte1

1 Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA

* To whom correspondence should be addressed. E-mail: marrelli{at}bcm.tmc.edu.

The present study evaluated the role of endothelial intermediate conductance calcium-sensitive K+ channels (IKCa) in the mechanism of endothelium-derived hyperpolarizing factor (EDHF)-mediated dilations in pressurized cerebral arteries. Male rat middle cerebral arteries (MCA) were mounted in an isolated vessel chamber, pressurized (85 mmHg), and luminally perfused (100 µl/min). Artery diameter was measured simultaneously with either endothelial [Ca2+]i (fura 2) or changes in endothelial membrane potential (di-8-ANEPPS). NOS and cyclooxygenase inhibitors were present throughout. Luminal application of UTP produced EDHF-mediated dilations that correlated with significant endothelial hyperpolarization. The dilation and endothelial hyperpolarization were virtually abolished by inhibitors of IKCa channels but not by selective inhibitors of small or large conductance KCa channels (apamin and iberiotoxin, respectively). Additionally, direct stimulation of endothelial IK channels with 1-EBIO produced endothelial hyperpolarization and vasodilatation that was blocked by inhibitors of IKCa channels. 1-EBIO hyperpolarized the endothelium but did not affect endothelial [Ca2+]i. We conclude that the mechanism of EDHF-mediated dilations in cerebral arteries requires stimulation of endothelial IKCa channels to promote endothelial hyperpolarization and subsequent vasodilatation.




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