Ischemic preconditioning (IPC) of one or two limbs improves performance of exercise that recruits the same limb(s). However, it is unclear whether IPC application to another limb than that in exercise is also effective and which mechanisms are involved. We investigated the effect of remote IPC (RIPC) on muscle fatigue, time to task failure, forearm hemodynamics, and deoxygenation during handgrip exercise. Thirteen men underwent RIPC in the lower limbs or a control intervention (CON), in random order, and then performed a constant load rhythmic handgrip protocol until task failure. Rates of contraction and relaxation (ΔForce/ΔTime) were used as indices of fatigue. Brachial artery blood flow and conductance, besides forearm microvascular deoxygenation, were assessed during exercise. RIPC attenuated the slowing of contraction and relaxation throughout exercise (P < 0.05 vs CON) and increased time to task failure by 11.2% (95% confidence interval: 0.7-21.7%, P <0.05 vs CON). There was no significant difference in blood flow, conductance, and deoxygenation between conditions throughout exercise (P > 0.05). In conclusion, RIPC applied to the lower limbs delayed the development of fatigue during handgrip exercise, prolonged time to task failure, but was not accompanied by changes in forearm hemodynamics and deoxygenation.

Overactivation of the renin-angiotensin (Ang) system (RAS) increases the classical arm (Ang-converting enzyme (ACE)/Ang II/Ang type 1 receptor (AT1R)) to the detriment of the protective arm (ACE2/Ang 1-7/Mas receptor (MasR)). The components of the RAS are present locally in white adipose tissue (WAT) and skeletal muscle, which act co-operatively, through specific mediators, in response to pathophysiological changes. In WAT, up-regulation of the classical arm promotes lipogenesis and reduces lipolysis and adipogenesis, leading to adipocyte hypertrophy and lipid storage, which are related to insulin resistance and increased inflammation. In skeletal muscle, the classical arm promotes protein degradation and increases the inflammatory status and oxidative stress, leading to muscle wasting. Conversely, the protective arm plays a counter-regulatory role by opposing the effect of Ang II. The accumulation of adipose tissue and muscle mass loss is associated with a higher risk of morbidity and mortality, which could be related, in part, to overactivation of the RAS. On the other hand, exercise training (ExT) shifts the balance of the RAS towards the protective arm, promoting the inhibition of the classical arm in parallel with the stimulation of the protective arm. Thus, fat mobilization and maintenance of muscle mass and function are facilitated. However, the mechanisms underlying exercise-induced changes in the RAS remain unclear. In this review, we present the RAS as a key mechanism of WAT and skeletal muscle metabolic dysfunction. Furthermore, we discuss the interaction between the RAS and exercise and the possible underlying mechanisms of the health-related aspects of ExT.

Middle cerebral artery mean velocity (MCAvmean) is attenuated with increasing age both at rest and during exercise. The aim of this study was to determine the influence of the age-dependent reduction in arterial PCO2 (PaCO2) and physical fitness herein. We administered supplemental CO2 (CO2 trial) or no additional gas (control trial) to the inspired air in a blinded and randomized manner, and assessed middle cerebral artery mean flow velocity during graded exercise in 1) 21 young [Y; age 24 Ϯ 3 yr (ϮSD)] volunteers of whom 11 were trained (YT) and 10 considered untrained (YUT), and 2) 17 old (O; 66 Ϯ 4 yr) volunteers of whom 8 and 9 were considered trained (OT) and untrained (OUT), respectively. A resting hypercapnic reactivity test was also performed. MCAvmean and PaCO2 were lower in O [44.9 Ϯ 3.1 cm/s and 30 Ϯ 1 mmHg (ϮSE)] compared with Y (59.3 Ϯ 2.3 cm/s and 34 Ϯ 1 mmHg, P Ͻ 0.01) at rest, independent of aerobic fitness level. The age-related decreases in MCAvmean and PaCO2 persisted during exercise. Supplemental CO2 reduced the age-associated decline in MCAv mean by 50%, suggesting that PaCO2 is a major component in the decline. On the other hand, relative hypercapnic reactivity was neither influenced by age (P ϭ 0.46) nor aerobic fitness (P ϭ 0.36). Although supplemental CO2 attenuated exercise-induced reduction in cerebral oxygenation (near-infrared spectroscopy), this did not influence exercise performance. In conclusion, PaCO2 contributes to the age-associated decline in MCAvmean at rest and during exercise; however exercise capacity did not diminish this age effect. brain blood flow; middle cerebral artery; old; transcranial Doppler CEREBRAL BLOOD FLOW (CBF) is meticulously regulated to ensure an adequate perfusion of the brain. With exercise middle cerebral artery mean velocity (MCAv mean ; a surrogate measure of CBF) is increased until ϳ60% of maximal oxygen uptake (V O 2max ) but thereafter declines toward resting levels (10,20,28). In young healthy individuals this drop in cerebral perfusion is likely the consequence of a hyperventilation facilitated reduction in PaCO 2 and hence augmented cerebral vasoconstriction (39). Accordingly, administration of CO 2 to the inspired air during exercise abolishes the decrease in MCAv mean (44,45), and during vigorous exercise MCAv mean is regulated by PaCO 2 and only to a lesser extent influenced by cerebral metabolism, mean arterial pressure (MAP), cardiac output, or sympathetic nerve activity (35).Compared with young healthy individuals a reduced CBF (24) and MCAv mean has consistently been reported in the aged population both at rest (2,7,9,15,25,27,49) and during exercise (9,10,28,32). Although a reduced MCAv mean response in aged humans is observed with exercise, its pattern follows that of young individuals, i.e., an initial increase which is then followed by a decline as the exercise intensity becomes intense (9,10,28,32). The regulating mechanisms for the reduction in CBF with age remain uncertain and global brain atrophy (11), decreased neuronal activ...

People with atrial fibrillation are at an increased risk of stroke, cognitive decline and dementia. We recently identified that individuals with atrial fibrillation exhibit a reduced cerebrovascular reactivity to carbon dioxide, indicative of a diminished cerebral vasodilatory reserve. In this study we sought to determine whether neurovascular coupling (NVC) is blunted in atrial fibrillation in comparison with age‐matched, hypertensive and healthy control participants. Posterior (PCA) and middle cerebral artery (MCA) flow velocity (Vm), along with beat‐to‐beat mean arterial pressure (MAP), were measured during a NVC assessment consisting of five cycles of visual stimulation (reading) for 30 s followed by 30 s with both eyes‐closed in 12 patients with atrial fibrillation (69 [7] yr; mean [SD], 3 women), 13 patients with hypertension (67 [5] yr, 4 women) and 12 healthy control participants (63 [10] yr, 4 women). Cerebrovascular conductance indices (CVCi) were calculated as PCA Vm/MAP and MCA Vm/MAP. NVC was denoted by the peak response observed during visual stimulation and is expressed as a percentage change from the eyes‐closed period. Resting PCA Vm and MCA Vm were not different between the atrial fibrillation (31 [7] and 49 [12] cm/s), hypertension (33 [8] and 55 [12] cm/s), and healthy control (36 [8] and 55 [12] cm/s) groups (P>0.05). Visual stimulation evoked an increase in PCA CVCi in all groups, but the magnitude of the hyperemic response was blunted in patients with atrial fibrillation (18 [8] %) and hypertension (17 [8] %), in comparison with healthy controls (26 [9] %) (P<0.05). Visual stimulation evoked a greater increase in MCA CVCi in the atrial fibrillation group (17 [6] %), than patients with hypertension (10 [4] %) and healthy controls (13 [6] %) (P<0.05). Thus, when peak PCA CVCi responses were considered following subtraction of the peak MCA CVCi responses (i.e., the “non‐selective” effect of the NVC test), a significantly diminished response was observed in the atrial fibrillation group (1 [8] %) compared the hypertension (7 [9] %) and healthy control groups (13 [9] %) (P<0.01). In summary, individuals with atrial fibrillation exhibit a blunted NVC response to visual stimulation when compared to age‐matched, healthy control and hypertensive participants. Additional studies are required to identify the mechanisms for the attenuated cerebral perfusion response of the occipital lobe to visual stimulation in atrial fibrillation (e.g., attenuated neuronal activation, altered cerebrovascular vasodilatory signaling). Support or Funding Information Funded by BHF project grant PG/15/45/31579. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

We sought to test the hypothesis that brain blood flow and cerebral vascular responsiveness to carbon dioxide (CVR ) are greater in aerobically trained young and old individuals compared to their untrained counterparts. In 11 young trained {[23 (20-26) years] [mean (95% confidence interval)]}, 10 young untrained [25 (22-28) years], 8 older trained [65 (61-69) years], and 9 older untrained [67 (64-71) years] healthy individuals, Doppler ultrasound of the internal carotid (ICA) and vertebral (VA) artery blood flow were determined, along with middle cerebral artery mean flow velocity (MCA V ). Bilateral ICA blood flow was higher in trained individuals when compared to untrained (≈31%, P < 0.05), but was not influenced by age. VA blood flow was not affected by age or cardiorespiratory fitness. MCA V was reduced with age [59.5 (55.0-64.1) cm/s young vs 43.6 (38.4-48.9) cm/s old, P < 0.05] with no significant effect of training observed. MCA CVR were not significantly affected by either age or training status, while ICA CVR tended to be elevated in the old trained group. These findings indicate that endurance training enhances bilateral ICA but not VA blood flow in both young and older individuals.

No abstract

Igor Braz received his medical degree from the Universidade Federal Fluminense in Rio de Janeiro state, Brazil. He is currently undertaking a PhD in human cerebrovascular control, at the University of Birmingham, UK, under the guidance of Dr James Fisher and Prof. Gregory Lip. In the future, he hopes to combine his passions of clinical practice and physiological research. James Fisher is currently a Senior Lecturer in Exercise Physiology in the School of Sport, Exercise and Rehabilitation Sciences at the University of Birmingham, UK. He works in the field of human cardiovascular control and his research seeks to better understand (1) the mechanisms underpinning the cardiovascular and cerebrovascular responses to exercise, and (2) the neural regulation of the heart and blood vessels in health and disease.This review was presented at the symposium "Ageing, physical activity and neurodegeneration", which took place at Ageing and Degeneration: A Physiological Perspective in Edinburgh, UK, 10-11 April 2015. Abstract Age is one of the most important risk factors for dementia and stroke. Examination of the cerebral circulatory responses to acute exercise in the elderly may help to pinpoint the mechanisms by which exercise training can reduce the risk of brain diseases, inform the optimization of exercise training programmes and assist with the identification of age-related alterations in cerebral vascular function. During low-to-moderate intensity dynamic exercise, enhanced neuronal activity is accompanied by cerebral perfusion increases of ß10-30%. Beyond ß60-70% maximal oxygen uptake, cerebral metabolism remains elevated but perfusion in the anterior portion of the circulation returns towards baseline, substantively because of a hyperventilation-mediated reduction in the partial pressure of arterial carbon dioxide (P aCO 2 ) and cerebral vasoconstriction. Cerebral perfusion is lower in older individuals, both at rest and during incremental dynamic exercise. Nevertheless, the increase in the estimated cerebral metabolic rate for oxygen and the arterial-internal jugular venous differences for glucose and lactate are similar in young and older individuals exercising at the same relative exercise intensities. Correction for the age-related reduction in P aCO 2 during exercise by the provision of supplementary CO 2 is suggested to remove ß50% of the difference in cerebral perfusion between young and older individuals. A multitude of candidates could account for the remaining difference, including cerebral atrophy, and enhanced vasoconstrictor and blunted vasodilatory pathways. In summary, age-related reductions in cerebral perfusion during exercise are partly associated with a lower P aCO 2 in exercising older individuals; nevertheless the cerebral extraction of glucose, lactate and oxygen appear to be preserved. Abstract figure legend Putative mechanisms explaining the impact of age on the cerebral blood flow (CBF) responses to exercise. CO 2 , carbon dioxide; CMRO 2 , cerebral metabolic rate of oxygen; %VO 2 max, maxima...

We investigated the effect of activating metabolically sensitive skeletal muscle afferents (muscle metaboreflex) on cerebral blood flow and the potentially confounding influence of concomitant changes in the partial pressure of arterial carbon dioxide. Eleven healthy males (25 ± 4 yr) performed submaximal leg cycling exercise on a semirecumbent cycle ergometer (heart rate: ∼120 beats/min), and assessments were made of the partial pressure of end-tidal carbon dioxide (PetCO2 ), internal carotid artery blood flow (ICAQ) and conductance (ICACVC), and middle cerebral artery mean blood velocity (MCAvm) and conductance index (MCACVCi).The muscle metaboreflex was activated during cycling with leg blood flow restriction (BFR) or isolated with postexercise ischemia (PEI). In separate trials, PetCO2 was either permitted to fluctuate spontaneously (control trial) or was clamped at 1 mmHg above resting levels (PetCO2 clamp trial). In the control trial, leg cycling with BFR decreased PetCO2 (Δ-4.8 ± 0.9 mmHg vs. leg cycling exercise) secondary to hyperventilation, while ICAQ, ICACVC, and MCAvm were unchanged and MCACVCi decreased. However, in the PetCO2 clamp trial, leg cycling with BFR increased both MCAvm (Δ5.9 ± 1.4 cm/s) and ICAQ (Δ20.0 ± 7.8 ml/min) and attenuated the decrease in MCACVCi, while ICACVC was unchanged. In the control trial, PEI decreased PetCO2 (Δ-7.0 ± 1.3 mmHg vs. rest), MCAvm and MCACVCi, whereas ICAQ and ICACVC were unchanged. In contrast, in the PetCO2 clamp trial both ICAQ (Δ18.5 ± 11.9 ml/min) and MCAvm (Δ8.8 ± 2.0 cm/s) were elevated, while ICACVC and MCACVCi were unchanged. In conclusion, when hyperventilation-related decreases in PetCO2 are prevented the activation of metabolically sensitive skeletal muscle afferent fibers increases cerebral blood flow.