Journal
JOURNAL OF VASCULAR RESEARCH
Volume 42, Issue 6, Pages 475-482Publisher
KARGER
DOI: 10.1159/000088101
Keywords
gap junctions; conducted dilation; hypercholesterolemia; nitric oxide; endothelium-derived hyperpolarizing factor
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Atherosclerosis and hyperlipidemia impair endothelium-dependent nitric oxide (NO)-mediated dilations in conducting arteries. In addition to NO, the endothelium releases an endothelium-derived hyperpolarizing factor (EDHF) in response to acetylcholine (ACh), which is particularly important in microvessels and initiates a dilation that conducts along the vessel through gap junctional communication. The expression of connexins is, however, altered by hypercholesterolemia. Therefore, we studied endothelium-dependent dilations and their conduction in murine hypercholesterolemic models. Dilations were assessed by intravital microscopy in arterioles with a diameter of similar to 35 mu m in ApoE and LDL receptor (LDLR-/-)-deficient mice after superfusion or locally confined application of ACh. ACh induced comparable concentration-dependent dilations in wild-type, LDLR-/-, and ApoE(-/-) mice fed a normal or high-cholesterol diet, however EC50 was slightly higher in ApoE(-/-) mice. Furthermore, the NO donor sodium-nitroprusside dilated arterioles to a similar extent ( similar to 60%). Locally initiated ACh dilations ( similar to 68%) conducted up to a distance of 1,100 mu m without significant attenuation even under severe hypercholesterolemic conditions. Since ACh dilation in the arterioles of mice is mainly mediated via EDHF, we conclude that hypercholesterolemia does not alter EDHF release and efficacy. This conclusion is confirmed by an intact conducted response since EDHF is a prerequisite for this response. The intact conduction also suggests that gap-junctional communication is functionally preserved in these models. Copyright (C) 2005 S. Karger AG, Basel.
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