Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Colorado State University, Fort Collins, CO 80523-1582, USA.
J Physiol. 2010 Oct 15;588(Pt 20):4017-27. doi: 10.1113/jphysiol.2010.197814.
Endothelium-dependent vasodilatation is reduced with advancing age in humans, as evidenced by blunted vasodilator responsiveness to acetylcholine (ACh). Circulating adenosine triphosphate (ATP) has been implicated in the control of skeletal muscle vascular tone during mismatches in oxygen delivery and demand (e.g. exercise) via binding to purinergic receptors (P2Y) on the endothelium evoking subsequent vasodilatation, and ageing is typically associated with reductions in muscle blood flow under such conditions. Therefore, we tested the hypothesis that ATP-mediated vasodilatation is impaired with age in healthy humans. We measured forearm blood flow (venous occlusion plethysmography) and calculated vascular conductance (FVC) responses to local intra-arterial infusions of ACh, ATP, and sodium nitroprusside (SNP) before and during ascorbic acid (AA) infusion in 13 young and 13 older adults. The peak increase in FVC to ACh was significantly impaired in older compared with young adults (262 ± 71% vs. 618 ± 97%; P < 0.05), and this difference was abolished during AA infusion (510 ± 82% vs. 556 ± 71%; not significant, NS). In contrast, peak FVC responses were not different between older and young adults to either ATP (675 ± 105% vs. 734 ± 126%) or SNP (1116 ± 111% vs. 1138 ± 148%) and AA infusion did not alter these responses in either age group (both NS). In another group of six young and six older adults, we determined whether vasodilator responses to adenosine and ATP were influenced by P1-receptor blockade via aminophylline. The peak FVC responses to adenosine were not different in young (350 ± 65%) versus older adults (360 ± 80%), and aminophylline blunted these responses by ∼50% in both groups. The peak FVC responses to ATP were again not different in young and older adults, and aminophylline did not impact the vasodilatation in either group. Thus, in contrast to the observed impairments in ACh responses, the vasodilatory response to exogenous ATP is not reduced with age in healthy humans. Further, our data also indicate that adenosine mediated vasodilatation is not reduced with age, and that ATP-mediated vasodilatation is independent of P1-receptor stimulation in both young and older adults.
内皮依赖性血管舒张随着人类年龄的增长而降低，这表现在乙酰胆碱（ACh）引起的血管舒张反应迟钝。循环三磷酸腺苷（ATP）已被牵连到在氧气输送和需求不匹配期间（例如运动）控制骨骼肌血管张力，通过结合内皮细胞上的嘌呤能受体（P2Y）引起随后的血管舒张，并且随着年龄的增长，在这种情况下，肌肉血流量通常会减少。因此，我们测试了这样一个假设，即在健康的人类中，随着年龄的增长，ATP 介导的血管舒张会受损。我们测量了前臂血流量（静脉闭塞体积描记法），并在 13 名年轻和 13 名老年人中计算了局部动脉内输注 ACh、ATP 和硝普钠（SNP）前后的血管传导率（FVC）反应，同时输注抗坏血酸（AA）。与年轻人相比，老年人的 FVC 对 ACh 的峰值增加明显受损（262 ± 71%对 618 ± 97%；P < 0.05），而在 AA 输注期间，这种差异被消除（510 ± 82%对 556 ± 71%；不显著，NS）。相比之下，在老年人和年轻人中，FVC 的峰值反应在 ATP（675 ± 105%对 734 ± 126%）或 SNP（1116 ± 111%对 1138 ± 148%）之间没有差异，AA 输注也没有改变这两个年龄组的这些反应（均为 NS）。在另一组 6 名年轻和 6 名老年成年人中，我们确定了通过氨茶碱阻断 P1 受体是否会影响腺苷和 ATP 的血管舒张反应。在年轻人（350 ± 65%）与老年人（360 ± 80%）中，腺苷的 FVC 峰值反应没有差异，而氨茶碱在两组中均使这些反应降低了约 50%。ATP 的 FVC 峰值反应在年轻人和老年人中再次没有差异，氨茶碱在两组中均不影响血管舒张。因此，与观察到的 ACh 反应受损相反，健康人类中，外源性 ATP 的血管舒张反应并没有随着年龄的增长而降低。此外，我们的数据还表明，随着年龄的增长，腺苷介导的血管舒张不会减少，并且在年轻人和老年人中，ATP 介导的血管舒张与 P1 受体刺激无关。
