title: Enhanced endothelin-1 system activity with overweight and obesity.
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.
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder 80309, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Weil
authors.forename: Christian M
authors.initials: CM
authors.lastname: Westby
authors.forename: Gary P
authors.initials: GP
authors.lastname: Van Guilder
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Greiner
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
authors.forename: Christopher A
authors.initials: CA
authors.lastname: DeSouza
mesh_terms: D050154:Adiposity; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000008:administration & dosage / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D050177:Overweight / Q000378:metabolism* / Q000503:physiopathology; D010456:Peptides, Cyclic / Q000008:administration & dosage; D044022:Receptor, Endothelin A / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D012044:Regression Analysis; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C072247:cyclo(Trp-Asp-Pro-Val-Leu)