Zurich Center for Integrative Human Physiology, Institute of Physiology, University of Zurich, Zurich, Switzerland.
Institute of Mountain Emergency Medicine, EURAC Research, Bolzano, Italy.
J Appl Physiol (1985). 2021 Dec 1;131(6):1824-1830. doi: 10.1152/japplphysiol.00505.2021. Epub 2021 Nov 4.
Exercise facilitates cerebral lactate uptake, likely by increasing arterial lactate concentration and hence the diffusion gradient across the blood-brain barrier. However, nonspecific β-adrenergic blockade by propranolol has previously reduced the arterio-jugular venous lactate difference (AV) during exercise, suggesting β-adrenergic control of cerebral lactate uptake. Alternatively, we hypothesized that propranolol reduces cerebral lactate uptake by decreasing arterial lactate concentration. To test that hypothesis, we evaluated cerebral lactate uptake taking changes in arterial concentration into account. Nine healthy males performed incremental cycling exercises to exhaustion with and without intravenous propranolol (18.7 ± 1.9 mg). Lactate concentration was determined in arterial and internal jugular venous blood at the end of each workload. To take changes in arterial lactate into account, we calculated the fractional extraction (FE) defined as AV divided by the arterial lactate concentration. Arterial lactate concentration was reduced by propranolol at any workload ( < 0.05), reaching 14 ± 3 and 11 ± 3 mmol·l during maximal exercise without and with propranolol, respectively. Although AV and FE increased during exercise (both < 0.05), they were both unaffected by propranolol at any workload ( = 0.68 and = 0.26) or for any given arterial lactate concentration ( = 0.78 and = 0.22). These findings support that while propranolol may reduce cerebral lactate uptake, this effect reflects the propranolol-induced reduction in arterial lactate concentration and not inhibition of a β-adrenergic mechanism within the brain. We hence conclude that cerebral lactate uptake during exercise is directly driven by the increasing arterial concentration with work rate. During exercise the brain consumes lactate as a substitute for glucose. Propranolol has previously attenuated this cerebral lactate uptake, suggesting a β-adrenergic transport mechanism. However, in the present study, we demonstrate that the fractional extraction of arterial lactate by the brain is unaffected by propranolol throughout incremental exercise to exhaustion. We conclude that cerebral lactate uptake during exercise is passively driven by the increasing arterial concentration, rather than by a β-adrenergic mechanism within the brain.
运动促进脑内乳酸摄取，可能是通过增加动脉内乳酸浓度，从而增加血脑屏障的扩散梯度。然而，普萘洛尔的非特异性β肾上腺素能阻断先前减少了运动期间的动静脉静脉乳酸差（AV），这表明β肾上腺素能控制脑内乳酸摄取。或者，我们假设普萘洛尔通过降低动脉内乳酸浓度来减少脑内乳酸摄取。为了验证该假设，我们评估了考虑动脉浓度变化时的脑乳酸摄取。9 名健康男性进行递增的踏车运动直至力竭，同时给予和不给予静脉内普萘洛尔（18.7±1.9mg）。在每个工作负荷结束时，测定动脉和颈内静脉内的乳酸浓度。为了考虑动脉乳酸浓度的变化，我们计算了定义为 AV 除以动脉乳酸浓度的分数提取（FE）。在任何工作负荷下，普萘洛尔均降低动脉乳酸浓度（<0.05），最大运动时分别达到 14±3 和 11±3mmol·l。尽管 AV 和 FE 在运动期间增加（均<0.05），但在任何工作负荷下（=0.68 和=0.26）或任何特定的动脉乳酸浓度下（=0.78 和=0.22），它们都不受普萘洛尔影响。这些发现支持这样的观点，即尽管普萘洛尔可能会减少脑内乳酸摄取，但这种效应反映了普萘洛尔诱导的动脉内乳酸浓度降低，而不是脑内β肾上腺素能机制的抑制。因此，我们得出结论，运动期间脑内乳酸摄取直接由工作速率增加的动脉浓度驱动。在运动期间，大脑消耗乳酸作为葡萄糖的替代品。普萘洛尔先前减弱了这种脑内乳酸摄取，表明存在β肾上腺素能转运机制。然而，在本研究中，我们表明，在递增运动直至力竭的整个过程中，脑内动脉乳酸的分数提取不受普萘洛尔的影响。我们得出结论，运动期间脑内乳酸摄取是由动脉浓度的增加被动驱动的，而不是由大脑内的β肾上腺素能机制驱动的。
