Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Vascular Physiology Research Group, Colorado State University, Fort Collins, USA.
Circ Res. 2012 Jul 6;111(2):220-30. doi: 10.1161/CIRCRESAHA.112.269571. Epub 2012 May 29.
Skeletal muscle blood flow is coupled with the oxygenation state of hemoglobin in young adults, whereby the erythrocyte functions as an oxygen sensor and releases ATP during deoxygenation to evoke vasodilation. Whether this function is impaired in humans of advanced age is unknown.
To test the hypothesis that older adults demonstrate impaired muscle blood flow and lower intravascular ATP during conditions of erythrocyte deoxygenation.
We showed impaired forearm blood flow responses during 2 conditions of erythrocyte deoxygenation (systemic hypoxia and graded handgrip exercise) with age, which was caused by reduced local vasodilation. In young adults, both hypoxia and exercise significantly increased venous [ATP] and ATP effluent (forearm blood flow×[ATP]) draining the skeletal muscle. In contrast, hypoxia and exercise did not increase venous [ATP] in older adults, and both venous [ATP] and ATP effluent were substantially reduced compared with young people despite similar levels of deoxygenation. Next, we demonstrated that this could not be explained by augmented extracellular ATP hydrolysis in whole blood with age. Finally, we found that deoxygenation-mediated ATP release from isolated erythrocytes was essentially nonexistent in older adults.
Skeletal muscle blood flow during conditions of erythrocyte deoxygenation was markedly reduced in aging humans, and reductions in plasma ATP and erythrocyte-mediated ATP release may be a novel mechanism underlying impaired vasodilation and oxygen delivery during hypoxemia with advancing age. Because aging is associated with elevated risk for ischemic cardiovascular disease and exercise intolerance, interventions that target erythrocyte-mediated ATP release may offer therapeutic potential.
在年轻人中，骨骼肌血流与血红蛋白的氧合状态相耦合，在此过程中，红细胞作为氧传感器，在脱氧时释放 ATP，以引发血管扩张。这种功能在高龄人群中是否受损尚不清楚。
测试以下假设，即老年人在红细胞脱氧条件下表现出肌肉血流受损和血管内 ATP 水平降低。
我们发现，随着年龄的增长，在两种红细胞脱氧条件（全身缺氧和分级握力运动）下，前臂血流反应受损，这是由于局部血管舒张减少所致。在年轻人中，缺氧和运动都会显著增加静脉 [ATP] 和从骨骼肌流出的 ATP 流出量（前臂血流×[ATP]）。相比之下，在老年人中，缺氧和运动并没有增加静脉 [ATP]，并且尽管脱氧程度相似，静脉 [ATP] 和 ATP 流出量与年轻人相比明显降低。接下来，我们证明这不能用全血中随年龄增加的细胞外 ATP 水解来解释。最后，我们发现老年人的脱氧介导的红细胞 ATP 释放基本上不存在。
在衰老过程中，人类的红细胞脱氧条件下的骨骼肌血流明显减少，血浆 ATP 和红细胞介导的 ATP 释放减少可能是衰老过程中低氧血症时血管舒张和氧输送受损的新机制。由于衰老与缺血性心血管疾病和运动不耐受的风险增加有关，针对红细胞介导的 ATP 释放的干预可能具有治疗潜力。
