title: Type 2 diabetes alters bone and marrow blood flow and vascular control mechanisms in the ZDF rat.
abstract: Bone health and cardiovascular function are compromised in individuals with type 2 diabetes mellitus (T2DM). The purpose of this study was to determine whether skeletal vascular control mechanisms are altered during the progression of T2DM in Zucker diabetic fatty (ZDF) rats. Responses of the principal nutrient artery (PNA) of the femur from obese ZDF rats with prediabetes, short-term diabetes, and long-term diabetes to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) vasodilation and potassium chloride, norepinephrine (NE), and a myogenic vasoconstrictor were determined in vitro. Few changes in the PNA vasomotor responses occurred for the prediabetic and short-term diabetic conditions. Endothelium-dependent and -independent vasodilation were reduced, and NE and myogenic vasoconstriction were increased in obese ZDF rats with long-term diabetes relative to lean age-matched controls. Differences in endothelium-dependent vasodilation of the femoral PNA between ZDF rats and controls were abolished by the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester. The passive pressure-diameter response of the femoral PNA was also lower across a range of intraluminal pressures with long-term T2DM. Regional bone and marrow perfusion and vascular conductance, measured in vivo using radiolabeled microspheres, were lower in obese ZDF rats with long-term diabetes. These findings indicate that the profound impairment of the bone circulation may contribute to the osteopenia found to occur in long bones during chronic T2DM.
authors.affiliation: Department of Applied Physiology and KinesiologyUniversity of Florida, Gainesville, Florida 32611, USADepartment of Kinesiology and Applied PhysiologyUniversity of Delaware, Newark, Delaware 19713, USADepartment of KinesiologyKansas State University, Manhattan, Kansas 66506, USADepartment of NutritionFood and Exercise Science, College of Human Sciences, Florida State University, 242 Sandels Building, 120 Convocation Way, Tallahassee, Florida 32306, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Stabley
authors.affiliation: Department of Applied Physiology and KinesiologyUniversity of Florida, Gainesville, Florida 32611, USADepartment of Kinesiology and Applied PhysiologyUniversity of Delaware, Newark, Delaware 19713, USADepartment of KinesiologyKansas State University, Manhattan, Kansas 66506, USADepartment of NutritionFood and Exercise Science, College of Human Sciences, Florida State University, 242 Sandels Building, 120 Convocation Way, Tallahassee, Florida 32306, USA.
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Prisby
authors.affiliation: Department of Applied Physiology and KinesiologyUniversity of Florida, Gainesville, Florida 32611, USADepartment of Kinesiology and Applied PhysiologyUniversity of Delaware, Newark, Delaware 19713, USADepartment of KinesiologyKansas State University, Manhattan, Kansas 66506, USADepartment of NutritionFood and Exercise Science, College of Human Sciences, Florida State University, 242 Sandels Building, 120 Convocation Way, Tallahassee, Florida 32306, USA Department of Applied Physiology and KinesiologyUniversity of Florida, Gainesville, Florida 32611, USADepartment of Kinesiology and Applied PhysiologyUniversity of Delaware, Newark, Delaware 19713, USADepartment of KinesiologyKansas State University, Manhattan, Kansas 66506, USADepartment of NutritionFood and Exercise Science, College of Human Sciences, Florida State University, 242 Sandels Building, 120 Convocation Way, Tallahassee, Florida 32306, USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Behnke
authors.affiliation: Department of Applied Physiology and KinesiologyUniversity of Florida, Gainesville, Florida 32611, USADepartment of Kinesiology and Applied PhysiologyUniversity of Delaware, Newark, Delaware 19713, USADepartment of KinesiologyKansas State University, Manhattan, Kansas 66506, USADepartment of NutritionFood and Exercise Science, College of Human Sciences, Florida State University, 242 Sandels Building, 120 Convocation Way, Tallahassee, Florida 32306, USA Department of Applied Physiology and KinesiologyUniversity of Florida, Gainesville, Florida 32611, USADepartment of Kinesiology and Applied PhysiologyUniversity of Delaware, Newark, Delaware 19713, USADepartment of KinesiologyKansas State University, Manhattan, Kansas 66506, USADepartment of NutritionFood and Exercise Science, College of Human Sciences, Florida State University, 242 Sandels Building, 120 Convocation Way, Tallahassee, Florida 32306, USA mdelp@fsu.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Delp
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology*; D001786:Blood Glucose; D001794:Blood Pressure; D001853:Bone Marrow / Q000098:blood supply*; D001842:Bone and Bones / Q000098:blood supply*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D009765:Obesity / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D001786:Blood Glucose
keywords: Zucker diabetic fatty rat; bone blood flow; diabetes; endothelium; vascular conductance
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