title: Impact of individual metabolic risk components or its clustering on endothelial and smooth muscle cell function in men.
abstract: BACKGROUND
  Impaired vasoreactivity is often observed in subjects with metabolic syndrome, a condition that includes the presence of a specific cluster of risk factors for obesity and cardiovascular disease. However, hierarchical causes in the impaired vasoreactivity have not been clarified. We evaluated the impact of individual metabolic risk components or its clustering under the condition of insulin resistance on endothelial and smooth muscle cell function.
  
  
  METHODS
  Vascular reactivity to acetylcholine (Ach), with or without nitric oxide synthase (NOS) inhibitor N (G)-monomethyl-L-arginine (L-NMMA), or sodium nitroprusside (SNP) by forearm venous occlusion plethysmography and insulin sensitivity index (M mg/kg/min) in euglycemic clamp were measured in men without (n = 18, control group) or with (n = 19, metabolic syndrome group) metabolic syndrome.
  
  
  RESULTS
  (1) Ach-induced maximal forearm blood flow (maxFBF) was impaired in subjects with metabolic syndrome. In particular, the NOS-dependent component of Ach-induced maxFBF was selectively decreased, while the NOS-independent component remained relatively unchanged. (2) Ach-induced maxFBF and ∆Ach-induced maxFBF with L-NMMA were correlated with waist circumference, glucose, and triglycerides, and most strongly correlated with visceral fat area, adiponectin, and M. (3) Multivariate regression analysis indicated that individual metabolic risk components explained Ach-induced maxFBF by 4-21 %. Clustering of all metabolic risk components increased this to 35 %, and the presence of metabolic syndrome explained 30 %, indicating that defining metabolic syndrome can effectively predict impairment of endothelial dysfunction.
  
  
  CONCLUSIONS
  Endothelial dysfunction was correlated with individual metabolic risk components, but more strongly with clustering of the components under a condition with low insulin sensitivity. We suggest that in subjects with metabolic syndrome, endothelial function is impaired by multiple cardiovascular risk factors exclusively when under the condition of insulin insensitivity and also that defining metabolic syndrome can effectively predict impairment of endothelial dysfunction.
authors.affiliation: Department of Cardio-Diabetes Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan. mshimabukuro-ur@umin.ac.jp.
authors.forename: Michio
authors.identifier: http://orcid.org/0000-0001-7835-7665
authors.initials: M
authors.lastname: Shimabukuro
authors.affiliation: Cardiovascular Department, Naha City Hospital, Okinawa, Japan.
authors.forename: Namio
authors.initials: N
authors.lastname: Higa
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki
authors.affiliation: Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ueda
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology*; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects; D012307:Risk Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D000109:Acetylcholine
keywords: Endothelial function; Insulin resistance; Metabolic syndrome; Obesity