Woodman Christopher R, Trott Daniel W, Laughlin M Harold
Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA.
J Appl Physiol (1985). 2007 Oct;103(4):1172-9. doi: 10.1152/japplphysiol.00416.2007. Epub 2007 Jul 12.
We tested the hypothesis that short-term increases in intraluminal pressure improve endothelium-dependent dilation and increase endothelial nitric oxide (NO) synthase (eNOS) expression in senescent soleus muscle feed arteries (SFA). SFA isolated from young (4 mo) and old (24 mo) Fischer 344 rats were cannulated and pressurized at 90 (p90) or 130 (p130) cmH(2)O for 4 h. At the end of the 4-h protocol, pressure in p130 SFA was lowered to 90 cmH(2)O for examination of endothelium-dependent (flow- or ACh-induced) vasodilation. Flow- and ACh-induced dilations were blunted in old p90 SFA relative to young p90 SFA. Pretreatment with increased pressure (p130) improved flow- and ACh-induced dilations in old SFA, such that vasodilator responses were similar to those in young SFA. In the presence of N(omega)-nitro-l-arginine (l-NNA) or l-NNA + indomethacin (Indo), flow-induced dilation was inhibited in old p130 SFA, such that the response was not greater than the response in old p90 SFA. In old p130 SFA, ACh-induced dilation was inhibited by l-NNA + Indo (not l-NNA alone). In a separate experiment, SFA were pressurized at 70, 90, 110, or 130 cmH(2)O for 4 h, and eNOS mRNA and protein content were assessed. Increased pressure induced eNOS mRNA expression in young (not old) SFA. eNOS protein content was not altered in young or old SFA. These results indicate that short-term increases in intraluminal pressure improve endothelium-dependent dilation in senescent SFA, in part by enhancing NO bioavailability; however, the beneficial effect was not associated with increased eNOS expression.
管腔内压力的短期升高可改善衰老比目鱼肌供血动脉（SFA）的内皮依赖性舒张，并增加内皮型一氧化氮（NO）合酶（eNOS）的表达。从年轻（4个月）和老年（24个月）的Fischer 344大鼠分离出SFA，插管后分别在90（p90）或130（p130）cmH₂O的压力下维持4小时。在4小时实验方案结束时，将p130组SFA的压力降至90 cmH₂O，以检测内皮依赖性（血流或乙酰胆碱诱导）的血管舒张。相对于年轻的p90组SFA，老年的p90组SFA中血流和乙酰胆碱诱导的舒张减弱。压力升高预处理（p130）可改善老年SFA中血流和乙酰胆碱诱导的舒张，使血管舒张反应与年轻SFA中的相似。在存在N（ω）-硝基-L-精氨酸（L-NNA）或L-NNA +吲哚美辛（Indo）的情况下，老年p130组SFA中血流诱导的舒张受到抑制，使得该反应不大于老年p90组SFA中的反应。在老年p130组SFA中，乙酰胆碱诱导的舒张受到L-NNA + Indo的抑制（单独的L-NNA则无此作用）。在另一个实验中，将SFA分别在70、90、110或130 cmH₂O的压力下维持4小时，并评估eNOS的mRNA和蛋白含量。压力升高诱导年轻（而非老年）SFA中eNOS mRNA的表达。年轻或老年SFA中eNOS蛋白含量均未改变。这些结果表明，管腔内压力的短期升高可改善衰老SFA的内皮依赖性舒张，部分原因是增强了NO的生物利用度；然而，这种有益作用与eNOS表达增加无关。
