Recently, dietary nitrate supplementation has been shown to improve exercise capacity in healthy individuals through a potential nitrate-nitrite-nitric oxide pathway. Nitric oxide has been shown to play an important role in compensatory vasodilation during exercise under hypoperfusion. Previously, we established that certain individuals lack a vasodilation response when perfusion pressure reductions compromise exercising muscle blood flow. Whether this lack of compensatory vasodilation in healthy, young individuals can be restored with dietary nitrate supplementation is unknown. Six healthy (21 ± 2 yr), recreationally active men completed a rhythmic forearm exercise. During steady-state exercise, the exercising arm was rapidly transitioned from an uncompromised (below heart) to a compromised (above heart) position, resulting in a reduction in local pressure of -31 ± 1 mmHg. Exercise was completed following 5 days of nitrate-rich (70 ml, 0.4 g nitrate) and nitrate-depleted (70 ml, ~0 g nitrate) beetroot juice consumption. Forearm blood flow (in milliliters per minute; brachial artery Doppler and echo ultrasound), mean arterial blood pressure (in millimeters of mercury; finger photoplethysmography), exercising forearm venous effluent (ante-cubital vein catheter), and plasma nitrite concentrations (chemiluminescence) revealed two distinct vasodilatory responses: nitrate supplementation increased (plasma nitrite) compared with placebo (245 ± 60 vs. 39 ± 9 nmol/l; < 0.001), and compensatory vasodilation was present following nitrate supplementation (568 ± 117 vs. 714 ± 139 ml ⋅ min ⋅ 100 mmHg; = 0.005) but not in placebo (687 ± 166 vs. 697 ± 171 min ⋅ 100 mmHg; = 0.42). As such, peak exercise capacity was reduced to a lesser degree (-4 ± 39 vs. -39 ± 27 N; = 0.01). In conclusion, dietary nitrate supplementation during a perfusion pressure challenge is an effective means of restoring exercise capacity and enabling compensatory vasodilation. Previously, we identified young, healthy persons who suffer compromised exercise tolerance when exercising muscle perfusion pressure is reduced as a result of a lack of compensatory vasodilation. The ability of nitrate supplementation to restore compensatory vasodilation in such noncompensators is unknown. We demonstrated that beetroot juice supplementation led to compensatory vasodilation and restored perfusion and exercise capacity. Elevated plasma nitrite is an effective intervention for correcting the absence of compensatory vasodilation in the noncompensator phenotype.
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http://dx.doi.org/10.1152/japplphysiol.00953.2016 | DOI Listing |
Sci Rep
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Department of Nephrology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
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Stichting Cardio Zorg, Kraayveld 5, 1171 JE Badhoevedorp, The Netherlands.
Introduction: Orthostatic intolerance is highly prevalent in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is caused by an abnormal reduction in cerebral blood flow (CBF). In healthy controls (HCs), the regulation of CBF is complex and cardiac output (CO) is an important determinant of CBF: a review showed that a 30% reduction in CO results in a 10% reduction in CBF. In previous and separate ME/CFS studies, we showed that CO and CBF decreased to a similar extent during tilt testing.
View Article and Find Full Text PDFKorean J Physiol Pharmacol
January 2025
Department of Physiology, Ajou University School of Medicine, Suwon 16499, Korea.
The brain's substantial metabolic requirements, consuming a substantial fraction of the body's total energy despite its relatively small mass, necessitate sophisticated metabolic mechanisms for efficient energy distribution and utilization. The astrocyte-neuron lactate shuttle (ANLS) hypothesis has emerged as a fundamental framework explaining the metabolic cooperation between astrocytes and neurons, whereby astrocyte-derived lactate serves as a crucial energy substrate for neurons. This review synthesizes current understanding of brain energy metabolism, focusing on the dual roles of lactate as both an energy substrate and a signaling molecule.
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January 2025
Division of Cardiology, Department of Medicine, Warren Alpert Medical School of Brown University, and Lifespan Cardiovascular Institute, Providence, Rhode Island, USA.
This state-of-the-art review describes the potential etiologies, pathophysiology, and management of mixed shock in the context of a proposed novel classification system. Cardiogenic-vasodilatory shock occurs when cardiogenic shock is complicated by inappropriate vasodilation, impairing compensatory mechanisms, and contributing to worsening shock. Vasodilatory-cardiogenic shock occurs when vasodilatory shock is complicated by myocardial dysfunction, resulting in low cardiac output.
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Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Background: Cognitive reserve allows for resilience to neuropathology, potentially through active compensation. Here, we examine ex vivo electrophysiological evidence for active compensation in Alzheimer's disease (AD) focusing on the cholinergic innervation of layer 6 in prefrontal cortex. Cholinergic pathways are vulnerable to neuropathology in AD and its preclinical models, and their modulation of deep layer prefrontal cortex is essential for attention and executive function.
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