体力活动维持肥胖 2 型糖尿病 OLETF 大鼠主动脉内皮依赖性舒张。
Physical activity maintains aortic endothelium-dependent relaxation in the obese type 2 diabetic OLETF rat.
机构信息
Dept. of Biomedical Sciences, Univ. of Missouri, E102 Veterinary Medicine Bldg., 1600 E. Rollins Rd., Columbia, MO 65211, USA.
出版信息
Am J Physiol Heart Circ Physiol. 2010 Jun;298(6):H1889-901. doi: 10.1152/ajpheart.01252.2009. Epub 2010 Mar 19.
We tested the hypothesis that physical activity can attenuate the temporal decline of ACh-induced endothelium-dependent relaxation during type 2 diabetes mellitus progression in the Otsuka Long-Evans Tokushima fatty (OLETF) rat. Sedentary OLETF rats exhibited decreased ACh-induced abdominal aortic endothelium-dependent relaxation from 13 to 20 wk of age (20-35%) and from 13 to 40 wk of age (35-50%). ACh-induced endothelium-dependent relaxation was maintained in the physically active OLETF group and control sedentary Long-Evans Tokushima Otsuka (LETO) group from 13 to 40 wk of age. Aortic pretreatment with N(G)-nitro-l-arginine (l-NNA), indomethacin (Indo), and l-NNA + Indo did not alter the temporal decline in ACh-induced endothelium-dependent relaxation. Temporal changes in the protein expression of SOD isoforms in the aortic endothelium or smooth muscle did not contribute to the temporal decline in ACh-induced endothelium-dependent relaxation in sedentary OLETF rats. A significant increase in the 40-wk-old sedentary LETO and physically active OLETF rat aortic phosphorylated endothelial nitric oxide (p-eNOS)-to-eNOS ratio was observed versus 13- and 20-wk-old rats in each group that was not seen in the 40- versus 13- and 20-wk-old sedentary OLETF rats. These results suggest that temporal changes in the antioxidant system, EDHF, and cycloxygenase metabolite production in sedentary OLETF rat aortas do not contribute to the temporal decline in sedentary OLETF rat aortic ACh-induced endothelium-dependent relaxation seen with type 2 diabetes mellitus progression. We also report that physical activity in conjunction with aging in the OLETF rat results in a temporal increase in the aortic endothelial p-eNOS-to-eNOS ratio that was not seen in sedentary OLETF rats. These results suggest that the sustained aortic ACh-induced endothelium-dependent relaxation in aged physically active OLETF rats may be the result of an increase in active aortic eNOS.
我们检验了一个假设，即体力活动可以减轻 2 型糖尿病进展过程中 Otsuka Long-Evans Tokushima 肥胖（OLETF）大鼠 ACh 诱导的内皮依赖性舒张的时间性下降。久坐不动的 OLETF 大鼠在 13 至 20 周龄（20-35%）和 13 至 40 周龄（35-50%）时表现出 ACh 诱导的腹主动脉内皮依赖性舒张减弱。在 13 至 40 周龄时，体力活动的 OLETF 组和对照久坐不动的 Long-Evans Tokushima Otsuka（LETO）组的 ACh 诱导的内皮依赖性舒张得到维持。主动脉预处理用 N(G)-硝基-L-精氨酸（l-NNA）、吲哚美辛（Indo）和 l-NNA+Indo 并不能改变 ACh 诱导的内皮依赖性舒张的时间性下降。主动脉内皮或平滑肌中 SOD 同工型的蛋白表达的时间变化并没有导致久坐不动的 OLETF 大鼠 ACh 诱导的内皮依赖性舒张的时间性下降。与每组 13 至 20 周龄的大鼠相比，40 周龄久坐不动的 LETO 和体力活动的 OLETF 大鼠的主动脉磷酸化内皮一氧化氮合酶（p-eNOS）与 eNOS 的比值显著增加，而 40 周龄久坐不动的 OLETF 大鼠与 13 周龄和 20 周龄的大鼠相比则没有这种情况。这些结果表明，久坐不动的 OLETF 大鼠主动脉抗氧化系统、EDHF 和环氧化酶代谢产物产生的时间变化与 2 型糖尿病进展中观察到的久坐不动的 OLETF 大鼠主动脉 ACh 诱导的内皮依赖性舒张的时间性下降无关。我们还报告说，在 OLETF 大鼠中，体力活动与衰老相结合会导致主动脉内皮 p-eNOS 与 eNOS 的比值随时间增加，而久坐不动的 OLETF 大鼠则没有这种情况。这些结果表明，年龄较大的体力活动的 OLETF 大鼠的主动脉 ACh 诱导的内皮依赖性舒张持续存在可能是由于主动脉活性 eNOS 的增加。
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