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Article
Enhanced Endothelin-1 System Activity with Overweight and Obesity
American Journal of Physiology. Heart and Circulatory Physiology
  • Brian R. Weil
  • Christian M. Westby
  • Gary Van Guilder
  • Jared J. Greiner
  • Brian L. Stauffer
  • Christopher A. DeSouza
Document Type
Article
Publication Date
9-1-2011
Abstract
Endothelin (ET)-1-mediated vasoconstrictor tone contributes to the development and progression of several adiposity-related conditions, including hypertension and atherosclerotic vascular disease. The aims of the present study were to determine 1) whether endogenous ET-1 vasoconstrictor activity is elevated in overweight and obese adults, and, if so, 2) whether increased ET-1-mediated vasoconstriction contributes to the adiposity-related impairment in endothelium-dependent vasodilation. Seventy-nine adults were studied: 34 normal weight [body mass index (BMI) < 25 kg/m(2)], 22 overweight (BMI ≥ 25 and < 30 kg/m(2)), and 23 obese (BMI ≥ 30 kg/m(2)). Forearm blood flow (FBF) responses to intra-arterial infusion of ET-1 (5 pmol/min for 20 min) and selective ET-1 receptor blockade (BQ-123, 100 nmol/min for 60 min) were determined. In a subset of the study population, FBF responses to ACh (4.0, 8.0, and 16.0 μg·100 ml tissue(-1)·min(-1)) were measured in the absence and presence of selective ET-1 receptor blockade. The vasoconstrictor response to ET-1 was significantly blunted in overweight and obese adults (∼ 70%) compared with normal weight adults. Selective ET-1 receptor blockade elicited a significant vasodilator response (∼ 20%) in overweight and obese adults but did not alter FBF in normal weight adults. Coinfusion of BQ-123 did not affect FBF responses to ACh in normal weight adults but resulted in an ∼ 20% increase (P < 0.05) in ACh-induced vasodilation in overweight and obese adults. These results demonstrate that overweight and obesity are associated with enhanced ET-1-mediated vasoconstriction that contributes to endothelial vasodilator dysfunction and may play a role in the increased prevalence of hypertension with increased adiposity.
PMCID
PMC3191085
DOI of Published Version
10.1152/ajpheart.00206.2011
Publisher
American Physiological Society
Citation Information
Brian R. Weil, Christian M. Westby, Gary Van Guilder, Jared J. Greiner, et al.. "Enhanced Endothelin-1 System Activity with Overweight and Obesity" American Journal of Physiology. Heart and Circulatory Physiology Vol. 301 Iss. 3 (2011) p. 689 - 695
Available at: http://works.bepress.com/gary-vanguilder/2/