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Nitric oxide synthase-dependent vasodilation of human subcutaneous arterioles correlates with noninvasive measurements of endothelial function. Am J Hypertens 2012 May;25(5):528-34

Date

02/18/2012

Pubmed ID

22337207

Pubmed Central ID

PMC3328603

DOI

10.1038/ajh.2012.8

Scopus ID

2-s2.0-84862791851   31 Citations

Abstract

BACKGROUND: Noninvasive measurements of endothelial function predict future adverse cardiovascular events, but offer limited opportunities for mechanistic insights into phenotypic observations. Subcutaneous adipose arterioles, accessible through minimally invasive methods, provide an opportunity for complimentary mechanistic studies. Limited data relating subcutaneous arteriolar endothelial function, cardiovascular risk factors, and noninvasive measurements of endothelial function currently exist.

METHODS: Forty-four subjects underwent noninvasive studies of endothelial function (brachial reactivity (flow-mediated dilation (FMD) and digital pulse arterial tonometry (PAT)) and measurements of endothelial-dependent vasodilation of gluteal subcutaneous arterioles to acetylcholine. Arteriolar endothelial function was measured (i) percent vasodilation to maximal acetylcholine dose (10(-5) mol/l) and (ii) total area under the curve (AUC) for the entire acetylcholine dose-response curve (total AUC-acetylcholine (Ach), doses 10(-10)-10(-5) mol/l).

RESULTS: Acetylcholine responses were almost completely nitric oxide (NO) dependent. Total AUC-Ach predicted FMD and PAT, but maximal acetylcholine vasodilation was not associated with these measures. A history of hypertension, diabetes, smoking, and low-density lipoprotein cholesterol levels were independent predictors of total AUC-Ach. In regression models, total AUC-Ach independently predicted FMD.

CONCLUSIONS: Acetylcholine vasodilator responses in human gluteal subcutaneous arterioles are NO synthase dependent and correlate with cardiac risk factors and in vivo measures of endothelial function. These data suggest subcutaneous arterioles offer an opportunity for translational studies of mechanisms of modulating NO bioavailability relevant to in vivo endothelial function measures.

Author List

Dharmashankar K, Welsh A, Wang J, Kizhakekuttu TJ, Ying R, Gutterman DD, Widlansky ME

Authors

David D. Gutterman MD Sr Associate Director, Professor in the Medicine department at Medical College of Wisconsin
Michael E. Widlansky MD Associate Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetylcholine
Adult
Arterioles
Brachial Artery
Diabetes Mellitus
Endothelium, Vascular
Female
Humans
Hypercholesterolemia
Hypertension
Male
Manometry
Middle Aged
Nitric Oxide Synthase
Regional Blood Flow
Retrospective Studies
Skin
Vasodilation
Vasodilator Agents
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d