Type 2 diabetes alters bone and marrow blood flow and vascular control mechanisms in the ZDF rat.

Bone health and cardiovascular function are compromised in individuals with type 2 diabetes mellitus (T2DM). The purpose of the present study was to determine whether skeletal vascular control mechanisms are altered during the progression of T2DM in the Zucker diabetic fatty (ZDF) rat. 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 KCl, norepinephrine and myogenic vasoconstrictor were determined in vitro. Few changes in the PNA vasomotor responses occurred in the pre-diabetic and short-term diabetic conditions. Endothelium-dependent and –independent vasodilation were reduced, and norepinephrine and myogenic vasoconstriction were enhanced 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 NG-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 suggest that the profound impairment of the bone circulation may contribute to the osteopenia found to occur in long bones with chronic T2DM.

2型糖尿病（T2DM）患者的骨骼健康和心血管功能受损。本研究的目的是确定在 Zucker糖尿病肥胖（ZDF）大鼠2型糖尿病进展过程中，骨骼血管控制机制是否发生改变。在体外测定了患有糖尿病前期、短期糖尿病和长期糖尿病的肥胖ZDF大鼠股骨主要营养动脉（PNA）对内皮依赖性（乙酰胆碱）和非依赖性（硝普钠）血管舒张以及对氯化钾、去甲肾上腺素和肌源性血管收缩的反应。在糖尿病前期和短期糖尿病状态下，PNA血管舒缩反应几乎没有变化。与年龄匹配的瘦对照组相比，患有长期糖尿病的肥胖ZDF大鼠内皮依赖性和非依赖性血管舒张减弱，去甲肾上腺素和肌源性血管收缩增强。一氧化氮合酶抑制剂NG - 硝基 - L - 精氨酸甲酯消除了ZDF大鼠和对照组之间股骨PNA内皮依赖性血管舒张的差异。在长期2型糖尿病的情况下，在一系列管腔内压力下，股骨PNA的被动压力 - 直径反应也较低。使用放射性微球在体内测量的局部骨骼和骨髓灌注以及血管传导性，在患有长期糖尿病的肥胖ZDF大鼠中较低。这些发现表明，骨循环的严重受损可能导致在慢性2型糖尿病的长骨中出现的骨质减少。