Hayward Reid, Ruangthai Ratree, Karnilaw Peter, Chicco Adam, Strange Robert, McCarty Heidi, Westerlind Kim C.
Department of Kinesiology, College of Health and Human Sciences, University of Northern Colorado, 80639, Greeley, CO, USA
Pathophysiology. 2003 Sep;9(4):207-214. doi: 10.1016/s0928-4680(03)00023-3.
Hyperhomocysteinemia is an independent risk factor for the development of cardiovascular disease. Exposure of endothelial cells to elevated levels of homocysteine (HCY) results in decreased availability of nitric oxide (NO) and impaired vascular function, both of which are early events in atherogenesis. Exercise training improves vascular function by increasing endothelial NO production secondary to an increase in the enzyme responsible for its synthesis, endothelial nitric oxide synthase (eNOS). We hypothesized that exercise training would increase endothelial NO production, which would attenuate the endothelial dysfunction associated with HCY exposure. Rats were randomly assigned to either sedentary (SED) or exercise (EX) groups. The exercise regimen consisted of treadmill running at 20-25 m/min, 15% grade, 30 min/day, 5 day/week for 6 weeks. Aortic rings obtained from SED and EX trained rats were incubated with 2 mM HCY for 120 min, then exposed to norepinephrine (NE 100 nM) to induce vasoconstriction. Once a stable contraction plateau was achieved, rings were exposed to increasing concentrations of the receptor-mediated endothelium-dependent vasodilator acetylcholine (ACh; 0.1, 1, 10, 100 nM). This procedure was repeated with the non-receptor-mediated endothelium-dependent vasodilator A-23187 (0.1, 1, 10, 100 nM), and the endothelium-independent vasodilator, NaNO(2) (0.1, 1, 10, 100 muM). In addition, eNOS protein content and eNOS enzyme activity were determined. Aortic rings obtained from exercise trained rats demonstrated significantly (P<0.05) greater relaxation to both ACh and A-23187 in comparison to aortic rings obtained from SED rats following exposure to HCY. Additionally, exercise training increased aortic eNOS protein content and activity. Our data demonstrate that exercise training improves endothelium-dependent vasorelaxation following HCY exposure and this may be due, at least in part, to elevated levels of eNOS protein and an increase in eNOS activity. These results suggest the possible role exercise may play in attenuating the endothelial dysfunction associated with hyperhomocysteinemia.
高同型半胱氨酸血症是心血管疾病发生的一个独立危险因素。内皮细胞暴露于高水平的同型半胱氨酸（HCY）会导致一氧化氮（NO）的可用性降低和血管功能受损，而这两者都是动脉粥样硬化发生过程中的早期事件。运动训练通过增加负责合成NO的酶——内皮型一氧化氮合酶（eNOS）的活性，进而增加内皮NO的生成，从而改善血管功能。我们推测运动训练会增加内皮NO的生成，这将减轻与HCY暴露相关的内皮功能障碍。将大鼠随机分为久坐组（SED）或运动组（EX）。运动方案包括在跑步机上以20 - 25米/分钟、坡度15%、每天30分钟、每周5天的速度跑步，持续6周。从SED组和EX组训练的大鼠获取主动脉环，用2 mM HCY孵育120分钟，然后用去甲肾上腺素（NE 100 nM）诱导血管收缩。一旦达到稳定的收缩平台，将主动脉环暴露于浓度递增的受体介导的内皮依赖性血管舒张剂乙酰胆碱（ACh；0.1、1、10、100 nM）。用非受体介导的内皮依赖性血管舒张剂A - 23187（0.1、1、10、100 nM）和内皮非依赖性血管舒张剂亚硝酸钠（NaNO₂；0.1、1、10、100 μM）重复此过程。此外，测定eNOS蛋白含量和eNOS酶活性。与暴露于HCY后的SED组大鼠的主动脉环相比，从运动训练的大鼠获取的主动脉环对ACh和A - 23187的舒张反应明显更大（P<0.05）。此外，运动训练增加了主动脉eNOS蛋白含量和活性。我们的数据表明，运动训练可改善HCY暴露后的内皮依赖性血管舒张，这可能至少部分归因于eNOS蛋白水平升高和eNOS活性增加。这些结果提示运动在减轻与高同型半胱氨酸血症相关的内皮功能障碍中可能发挥的作用。
