title: Impaired endothelium independent vasodilation in the cutaneous microvasculature of young obese adults.
abstract: Microvascular dysfunction contributes to the development of cardiovascular and metabolic disease. This study tested the hypothesis that young obese (BMI>30 kg m(-2)), otherwise healthy, adults (N=15) have impaired microvascular function relative to age and sex matched, lean (BMI<25 kg m(-2)) individuals (N=14). Participants were instrumented with two microdialysis probes in the cutaneous vasculature of one forearm; one for a wide dose range of infusions of the endothelium-dependent vasodilator methacholine (MCh) and the other for the endothelium-independent vasodilator sodium nitroprusside (SNP). Local temperature at each site was clamped at 33 °C and cutaneous blood flow was indexed by laser Doppler flowmetry (LDF). LDF was recorded while 7 doses of each drug (MCh: 10(-6)-1M; SNP: 5 × 10(-8)-5 × 10(-2)M) were infused at a rate of 2 μl/min for 8 min per dose. Both sites finished with heating to 43 °C and 5 × 10(-2)M SNP to achieve site specific maximal vasodilation. Mean arterial blood pressure (MAP) was assessed in the last minute of each dose and was used for subsequent calculation of cutaneous vascular conductance (CVC; LDF/MAP) and responses were normalized to each individual site's maximal response (%CVCmax). Group four-parameter dose response curves were compared with an extra sum of squares F-test. SNP EC50 was greater in obese relative to lean (-2.931 ± 0.10 vs -3.746 ± 0.18 Log[SNP]M, P<0.001); however, there was no difference in MCh EC50 between groups (-3.796 ± 0.23 vs -3.852 ± 0.25 Log[MCh]M, P=0.81). Additionally, baseline and maximal CVC in both sites were similar between groups (all P>0.05). These results suggest attenuated endothelium-independent response to nitric oxide while endothelium-dependent vasodilation function is maintained.
authors.affiliation: Environmental and Autonomic Physiology Laboratory, Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Jordan C
authors.initials: JC
authors.lastname: Patik
authors.affiliation: Environmental and Autonomic Physiology Laboratory, Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Christmas
authors.affiliation: Environmental and Autonomic Physiology Laboratory, Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Chansol
authors.initials: C
authors.lastname: Hurr
authors.affiliation: Environmental and Autonomic Physiology Laboratory, Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, Texas, USA. Electronic address: matthew.brothers@uta.edu.
authors.forename: R Matthew
authors.initials: RM
authors.lastname: Brothers
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D017551:Microdialysis; D055806:Microvessels / Q000187:drug effects / Q000503:physiopathology; D009599:Nitroprusside / Q000008:administration & dosage; D009765:Obesity / Q000503:physiopathology*; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D014665:Vasodilator Agents; D016210:Methacholine Chloride; D009599:Nitroprusside
keywords: Endothelium-independent; Microdialysis; Microvascular; Nitric oxide; Obesity; Sodium nitroprusside