title: Blunted temporal activity of microvascular perfusion heterogeneity in metabolic syndrome: a new attractor for peripheral vascular disease?
abstract: A key clinical outcome for peripheral vascular disease (PVD) in patients is a progressive decay in skeletal muscle performance and its ability to resist fatigue with elevated metabolic demand. We have demonstrated that PVD in obese Zucker rats (OZR) is partially due to increased perfusion distribution heterogeneity at successive microvascular bifurcations within skeletal muscle. As this increased heterogeneity (γ) is longitudinally present in the network, its cumulative impact is a more heterogeneous distribution of perfusion between terminal arterioles than normal, causing greater regional tissue ischemia. To minimize this negative outcome, a likely compensatory mechanism against an increased γ should be an increased temporal switching at arteriolar bifurcations to minimize downstream perfusion deficits. Using in situ cremaster muscle, we determined that temporal activity (the cumulative sum of absolute differences between successive values of γ, taken every 20 s) was lower in OZR than in control animals, and this difference was present in both proximal (1A-2A) and distal (3A-4A) arteriolar bifurcations. Although adrenoreceptor blockade (phentolamine) improved temporal activity in 1A-2A arteriolar bifurcations in OZR, this was without impact in the distal microcirculation, where only interventions against oxidant stress (Tempol) and thromboxane A(2) activity (SQ-29548) were effective. Analysis of the attractor for γ indicated that it was not only elevated in OZR but also exhibited severe reductions in range, suggesting that the ability of the microcirculation to respond to any challenge is highly restricted and may represent the major contributor to the manifestation of poor muscle performance at this age in OZR.
authors.affiliation: Department of Physiology and Pharmacology and Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Butcher
authors.forename: Adam G
authors.initials: AG
authors.lastname: Goodwill
authors.forename: Shyla C
authors.initials: SC
authors.lastname: Stanley
authors.forename: Jefferson C
authors.initials: JC
authors.lastname: Frisbee
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003497:Cyclic N-Oxides / Q000627:therapeutic use; D004195:Disease Models, Animal; D005231:Fatty Acids, Unsaturated; D006801:Humans; D006834:Hydrazines / Q000627:therapeutic use; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D055806:Microvessels / Q000187:drug effects / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D009765:Obesity / Q000150:complications / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016491:Peripheral Vascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D010646:Phentolamine / Q000627:therapeutic use; D051381:Rats; D011924:Rats, Zucker; D013113:Spin Labels
chemical_list: D000317:Adrenergic alpha-Antagonists; D000975:Antioxidants; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003497:Cyclic N-Oxides; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D013113:Spin Labels; C045749:SQ 29548; C001803:tempol; D010646:Phentolamine