Objective: This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without cardiovascular autonomic neuropathy (CAN). Methodology: A systematic review of randomized and nonrandomized clinical studies characterizing reactive hyperemia and autonomic activity in type 2 diabetes patients with and without CAN was performed. Results: Five articles showed differences in RH between healthy subjects and diabetic patients with and/or without neuropathy, while one study did not show such differences between healthy subjects and diabetic patients, but patients with diabetic ulcers had lower RH index values compared to healthy controls. Another study found no significant difference in blood flow after a muscle strain that induced reactive hyperemia between normal subjects and non-smoking diabetic patients. Four studies measured reactive hyperemia using peripheral arterial tonometry (PAT); only two found a significantly lower endothelial-function-derived measure of PAT in diabetic patients than in those without CAN. Four studies measured reactive hyperemia using flow-mediated dilation (FMD), but no significant differences were reported between diabetic patients with and without CAN. Two studies measured RH using laser Doppler techniques; one of them found significant differences in the blood flow of calf skin after stretching between diabetic non-smokers and smokers. The diabetic smokers had neurogenic activity at baseline that was significantly lower than that of the normal subjects. The greatest evidence revealed that the differences in RH between diabetic patients with and without CAN may depend on both the method used to measure hyperemia and that applied for the ANS examination as well as the type of autonomic deficit present in the patients. Conclusions: In diabetic patients, there is a deterioration in the vasodilator response to the reactive hyperemia maneuver compared to healthy subjects, which depends in part on endothelial and autonomic dysfunction. Blood flow alterations in diabetic patients during RH are mainly mediated by sympathetic dysfunction. The greatest evidence suggests a relationship between ANS and RH; however, there are no significant differences in RH between diabetic patients with and without CAN, as measured using FMD. When the flow of the microvascular territory is measured, the differences between diabetics with and without CAN become evident. Therefore, RH measured using PAT may reflect diabetic neuropathic changes with greater sensitivity compared to FMD.

Reactive hyperemia is a well-established technique for the non-invasive evaluation of the peripheral microcirculatory function, measured as the magnitude of limb re-perfusion after a brief period of ischemia. Despite widespread adoption by researchers and clinicians alike, many uncertainties remain surrounding interpretation, compounded by patient-specific confounding factors (such as blood pressure or the metabolic rate of the ischemic limb). Mathematical modeling can accelerate our understanding of the physiology underlying the reactive hyperemia response and guide in the estimation of quantities which are difficult to measure experimentally. In this work, we aim to provide a comprehensive guide for mathematical modeling techniques that can be used for describing the key phenomena involved in the reactive hyperemia response, alongside their limitations and advantages. The reported methodologies can be used for investigating specific reactive hyperemia aspects alone, or can be combined into a computational framework to be used in (pre-)clinical settings.

Previous studies have investigated the impact of dietary nitrate on vascular function due to the association between dietary nitrate ingestion and improvement in nitric oxide (NO) bioavailability. Considering that NO can present different effects through vascular beds (macro- vs. microvasculature) due to the specific characteristic (function and morphology) that each vessel exhibits, it is crucial to investigate the effect of dietary nitrate ingestion on the macro- and microvascular function to understand the effect of nitrate on vascular function. For this reason, this review aimed to evaluate the impact of dietary nitrate on macro- and microvascular function in humans. A total of 29 studies were included in the systematic review, of which 19 studies evaluated the effect of nitrate supplementation on macrovascular function, eight studies evaluated the effect on microvascular function, and two studies evaluated the impact on both macro- and microvascular function. The literature suggests that dietary nitrate ingestion seems to improve the vascular function in macrovasculature, whereas microvascular function appears to be modest. Future studies investigating the effect of nitrate ingestion on vascular function should focus on measuring macro- and microvascular function whenever possible so that the impact of nitrate-rich foods on vascular segments could be better understood.

BACKGROUND: Aging is an independent risk factor for cardiovascular events. It promotes vascular dysfunction which is associated with risk factors for cardiovascular diseases (CVDs). Exercise can modulate vascular function parameters, but little is known about the effects of different modalities of training (aerobic, resistance, and combined) on endothelial function and arterial stiffness in older adults.
METHODS: This systematic review study will include randomized controlled trials (RCTs) selected from the electronic databases MEDLINE (PubMed), Cochrane, LILACS, EMBASE, and Web of Science. We will follow the PRISMA guidelines and PICOS framework. Studies involving both male and female older adults (≥60 years old) with or without comorbidities undergoing aerobic, resistance, and/or combined training compared to a control group (no exercise) will be eligible. We will use the Cochrane Risk of Bias 2 (RoB 2) tool to evaluate the quality of individual studies and GRADE to assess the strength of evidence. Statistical analyses will be conducted with RStudio for Windows (v1.3.959) using R package meta.
CONCLUSIONS: A systematic review and meta-analysis involving data from studies of older adults would deepen our understanding of vascular adaptations to exercise training in this population. It could provide new insights into how health providers can improve patient management and prevention of cardiovascular events in older adults.
BACKGROUND: PROSPERO 42021275451.

Reactive hyperemia is a well-established technique for noninvasive assessment of peripheral microvascular function and a predictor of all-cause and cardiovascular morbidity and mortality. In its simplest form, reactive hyperemia represents the magnitude of limb reperfusion following a brief period of ischemia induced by arterial occlusion. Over the past two decades, investigators have employed a variety of methods, including brachial artery velocity by Doppler ultrasound, tissue reperfusion by near-infrared spectroscopy, limb distension by venous occlusion plethysmography, and peripheral artery tonometry, to measure reactive hyperemia. Regardless of the technique used to measure reactive hyperemia, blunted reactive hyperemia is believed to reflect impaired microvascular function. With the advent of several technological advancements, together with an increased interest in the microcirculation, reactive hyperemia is becoming more common as a research tool and is widely used across multiple disciplines. With this in mind, we sought to review the various methodologies commonly used to assess reactive hyperemia and current mechanistic pathways believed to contribute to reactive hyperemia and reflect on several methodological considerations.