Department of Biomedical Sciences, Florida State University , Tallahassee, Florida.
Department of Physiology and Functional Genomics, University of Florida , Gainesville, Florida.
J Appl Physiol (1985). 2018 Jan 1;124(1):140-149. doi: 10.1152/japplphysiol.00459.2017. Epub 2017 Oct 12.
Coronary microvascular function and blood flow responses during acute exercise are impaired in the aged heart but can be restored by exercise training. Coronary microvascular resistance is directly dependent on vascular smooth muscle function in coronary resistance arterioles; therefore, we hypothesized that age impairs contractile function and alters the phenotype of vascular smooth muscle in coronary arterioles. We further hypothesized that exercise training restores contractile function and reverses age-induced phenotypic alterations of arteriolar smooth muscle. Young and old Fischer 344 rats underwent 10 wk of treadmill exercise training or remained sedentary. At the end of training or cage confinement, contractile responses, vascular smooth muscle proliferation, and expression of contractile proteins were assessed in isolated coronary arterioles. Both receptor- and non-receptor-mediated contractile function were impaired in coronary arterioles from aged rats. Vascular smooth muscle shifted from a differentiated, contractile phenotype to a secretory phenotype with associated proliferation of smooth muscle in the arteriolar wall. Expression of smooth muscle myosin heavy chain 1 (SM1) was decreased in arterioles from aged rats, whereas expression of phospho-histone H3 and of the synthetic protein ribosomal protein S6 (rpS6) were increased. Exercise training improved contractile responses, reduced smooth muscle proliferation and expression of rpS6, and increased expression of SM1 in arterioles from old rats. Thus age-induced contractile dysfunction of coronary arterioles and emergence of a secretory smooth muscle phenotype may contribute to impaired coronary blood flow responses, but arteriolar contractile responsiveness and a younger smooth muscle phenotype can be restored with late-life exercise training. NEW & NOTEWORTHY Aging impairs contractile function of coronary arterioles and induces a shift of the vascular smooth muscle toward a proliferative, noncontractile phenotype. Late-life exercise training reverses contractile dysfunction of coronary arterioles and restores a young phenotype to the vascular smooth muscle.
在衰老的心脏中，急性运动期间的冠状动脉微血管功能和血流反应受损，但运动训练可以恢复。冠状动脉微血管阻力直接取决于冠状动脉阻力小动脉中的血管平滑肌功能；因此，我们假设年龄会损害收缩功能并改变冠状动脉小动脉中血管平滑肌的表型。我们进一步假设，运动训练可以恢复收缩功能并逆转血管平滑肌的年龄诱导表型改变。年轻和年老的 Fischer 344 大鼠接受了 10 周的跑步机运动训练或保持久坐不动。在训练结束或笼中限制时，评估了分离的冠状动脉小动脉中的收缩反应、血管平滑肌增殖和收缩蛋白的表达。受体和非受体介导的收缩功能在年老大鼠的冠状动脉小动脉中均受损。血管平滑肌从分化的收缩表型转变为分泌表型，伴有小动脉壁中平滑肌的增殖。年老大鼠的血管平滑肌肌球蛋白重链 1（SM1）的表达减少，而磷酸化组蛋白 H3 和合成蛋白核糖体蛋白 S6（rpS6）的表达增加。运动训练改善了收缩反应，减少了平滑肌增殖和 rpS6 的表达，并增加了年老大鼠小动脉中 SM1 的表达。因此，年龄引起的冠状动脉小动脉收缩功能障碍和分泌型平滑肌表型的出现可能导致冠状动脉血流反应受损，但晚期生命运动训练可以恢复小动脉的收缩反应性和更年轻的平滑肌表型。新的和值得注意的是，衰老会损害冠状动脉小动脉的收缩功能，并导致血管平滑肌向增殖性非收缩表型转变。晚年运动训练可以逆转冠状动脉小动脉的收缩功能障碍，并使血管平滑肌恢复年轻表型。
