Lemaster Kent, Jackson Dwayne, Welsh Donald G, Brooks Steven D, Chantler Paul D, Frisbee Jefferson C
Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, WV, USA.
Microcirculation. 2017 Feb;24(2). doi: 10.1111/micc.12349.
Although studies suggest elevated adrenergic activity paralleling metabolic syndrome in OZRs, the moderate hypertension and modest impact on organ perfusion question the multi-scale validity of these data.
To understand how adrenergic function contributes to vascular reactivity in OZR, we utilized a multi-scale approach to investigate pressure responses, skeletal muscle blood flow, and vascular reactivity following adrenergic challenge.
For OZR, adrenergic challenge resulted in increased pressor responses vs LZRs, mediated via α receptors, with minimal contribution by either ROS or NO bioavailability. In situ gastrocnemius muscle of OZR exhibited blunted functional hyperemia, partially restored with α inhibition, although improved muscle performance and VO required combined treatment with TEMPOL. Within OZR in situ cremaster muscle, proximal arterioles exhibited a more heterogeneous constriction to adrenergic challenge, biased toward hyperresponsiveness, vs LZR. This increasingly heterogeneous pattern was mirrored in ex vivo arterioles, mediated via α receptors, with roles for ROS and NO bioavailability evident in hyperresponsive vessels only.
These results support the central role of the α adrenoreceptor for augmented pressor responses and elevations in vascular resistance, but identify an increased heterogeneity of constrictor reactivity in OZR that is presently of unclear purpose.
尽管研究表明OZRs（肥胖 Zucker 大鼠）中肾上腺素能活性升高与代谢综合征平行，但中度高血压以及对器官灌注的适度影响对这些数据的多尺度有效性提出了质疑。
为了解肾上腺素能功能如何影响OZR的血管反应性，我们采用多尺度方法研究了肾上腺素能刺激后的压力反应、骨骼肌血流量和血管反应性。
对于OZR，肾上腺素能刺激导致与LZRs（瘦 Zucker 大鼠）相比升压反应增加，通过α受体介导，ROS或NO生物利用度的贡献最小。OZR的原位腓肠肌表现出功能性充血减弱，α抑制可部分恢复，尽管改善肌肉性能和VO2需要与TEMPOL联合治疗。在OZR的原位提睾肌中，近端小动脉对肾上腺素能刺激表现出更不均匀的收缩，与LZR相比偏向于高反应性。这种越来越不均匀的模式在离体小动脉中也有体现，通过α受体介导，仅在高反应性血管中ROS和NO生物利用度起作用。
这些结果支持α肾上腺素能受体在增强升压反应和血管阻力升高中的核心作用，但发现OZR中收缩反应性的异质性增加，目前其目的尚不清楚。
