HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/1/H447    most recent 01298.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by VanTeeffelen, J. W. G. E. Articles by Spaan, J. A. E. Search for Related Content PubMed PubMed Citation Articles by VanTeeffelen, J. W. G. E. Articles by Spaan, J. A. E.

Hypercholesterolemia impairs reactive hyperemic vasodilation of 2A but not 3A arterioles in mouse cremaster muscle

Department of Medical Physics, Cardiovascular Research Institute Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Submitted 23 December 2004 ; accepted in final form 16 February 2005

Hypercholesterolemia and atherosclerosis have been associated with changes in the microvasculature, in particular with endothelial dysfunction. In the present study, the impact of atherogenic conditions on arteriolar vasomotor control was determined. Arteriolar [second-order (2A) and third-order (3A) arterioles; diameter range: 9–37 µm] responses during reactive hyperemia (RH) were determined in cremaster muscle of anesthetized mice. C57Bl/6 mice on normal rodent chow were used as controls and high-fat/high-cholesterol (HFC)-fed C57Bl/6 and ApoE3-Leiden mice as hypercholesterolemic mice. The HFC diet resulted in time-dependent increases in plasma cholesterol and triglyceride concentrations (P < 0.001), which were more pronounced in ApoE3-Leiden mice (P < 0.001). In control mice, inhibition of nitric oxide (NO) synthesis with N-nitro-L-arginine (L-NNA) reduced baseline diameter from 17.9 ± 1.2 to 15.9 ± 1.3 µm (P < 0.05) and decreased the duration of RH [time to 50% (t₅₀) of recovery: 23.3 ± 3.6 vs. 12.5 ± 1.3 s (P = 0.003)]. t₅₀ was longer in 2A versus 3A arterioles (33 ± 3 vs. 18 ± 2 s, P < 0.001) and increased with wall shear rate at the beginning of RH in 2A arterioles only. Compared with control mice, RH duration was reduced in 2A arterioles of HFC mice (t₅₀: 11 ± 2 s, P < 0.001 vs. control) but not affected in 3A vessels. L-NNA did not affect baseline diameter in HFC mice and reduced t₅₀ only in "slow" responders (t₅₀ 10 s). It is concluded that hypercholesterolemia results in an impairment of NO-mediated vasomotor control in 2A but not 3A arterioles during dynamic changes of perfusion like RH. 2A arterioles likely therefore represent the functional locus of endothelial dysfunction during atherogenic conditions.

endothelial dysfunction; shear-dependent dilation; arteriolar heterogeneity; ApoE3-Leiden

This article has been cited by other articles:

				J. W. G. E. VanTeeffelen, A. A. Constantinescu, J. Brands, J. A. E. Spaan, and H. Vink Bradykinin- and sodium nitroprusside-induced increases in capillary tube haematocrit in mouse cremaster muscle are associated with impaired glycocalyx barrier properties J. Physiol., July 1, 2008; 586(13): 3207 - 3218. [Abstract] [Full Text] [PDF]

				T. Yada, H. Shimokawa, K. Morikawa, A. Takaki, Y. Shinozaki, H. Mori, M. Goto, Y. Ogasawara, and F. Kajiya Role of Cu,Zn-SOD in the synthesis of endogenous vasodilator hydrogen peroxide during reactive hyperemia in mouse mesenteric microcirculation in vivo Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H441 - H448. [Abstract] [Full Text] [PDF]

				J. W.G.E. VanTeeffelen, J. Brands, C. Jansen, J. A.E. Spaan, and H. Vink Heparin Impairs Glycocalyx Barrier Properties and Attenuates Shear Dependent Vasodilation in Mice Hypertension, July 1, 2007; 50(1): 261 - 267. [Abstract] [Full Text] [PDF]

				W. F. Jackson Silent Inward Rectifier K+ Channels in Hypercholesterolemia Circ. Res., April 28, 2006; 98(8): 982 - 984. [Full Text] [PDF]