Despite positive outcomes of transcutaneous vagus nerve stimulation (tVNS) via the auricular branch of the vagus nerve (ABVN), the mechanisms underlying these outcomes remain unclear. Additionally, previous studies have not been controlled the possible placebo effects of tVNS. To test the hypothesis that tVNS acutely improves spontaneous cardiac baroreflex sensitivity (cBRS) and autonomic modulation, and that these effects are specific to stimulation of ABVN. Thirteen healthy men (23±1yrs) were randomized across three experimental visits. In active tVNS, electrodes were placed on the tragus of the ear and electrical current was applied by using a Transcutaneous Electrical Nerve Stimulation device. A time-control visit was performed with the electrodes placed on tragus, but no current was applied (sham-T). Additionally, to avoid a placebo effect, another sham protocol was performed with same electrical current of the active visit, but the electrodes were placed on the ear lobe (an area without cutaneous nerve endings from the vagus - tLS). Beat-to-beat heart rate (HR) and blood pressure (BP) were monitored at rest, during stimulation (active, sham-T and tLS) and recovery. cBRS was measured via sequence technique. Both HR (HRV) and BP variability (BPV) were also measured. Arterial BP and BPV were not affected by any active or sham protocols (P > 0.05). Resting HR and LF/HF ratio of HRV decreased (Δ-3.4 ± 1% and Δ-15 ± 12%, P < 0.05, respectively) and cBRS increased (Δ24 ± 8%, P < 0.05) during active tVNS, but were unchanged during both sham protocols. tVNS acutely improves cBRS and autonomic modulation in healthy young men.

Ischemic preconditioning (IPC) has been shown to improve performance of exercises lasting 10–90 s (anaerobic) and more than 90 s (aerobic). However, its effect on repeated sprint performance has been controversial, placebo effect has not been adequately controlled, and nocebo effect has not been avoided. Thus, the IPC effect on repeated sprint performance was investigated using a swimming task and controlling placebo/nocebo effects. Short-distance university swimmers were randomized to two groups. One group (n = 15, 24 ± 1 yr [mean ± SEM]) was exposed to IPC (ischemia cycles lasted 5 min) and control (CT) (no ischemia); another (n = 15, 24 ± 1 yr) to a placebo intervention (SHAM) (ischemia cycles lasted 1 min) and CT. Seven subjects crossed over groups. Subjects were informed IPC and SHAM would improve performance compared with CT and would be harmless despite circulatory occlusion sensations. The swimming task consisted of six 50-m all-out efforts repeated every 3 min. IPC, in contrast with SHAM, reduced worst sprint time (IPC, 35.21 ± 0.73 vs CT, 36.53 ± 0.72 s; P = 0.04) and total sprints time (IPC, 203.7 ± 4.60 vs CT, 206.03 ± 4.57 s; P = 0.02), moreover augmented swimming velocity (IPC, 1.45 ± 0.03 vs CT, 1.44 ± 0.03 m·s−1; P = 0.049). Six of seven subjects who crossed over groups reduced total sprints time with IPC versus SHAM (delta = −3.95 ± 1.49 s, P = 0.09). Both IPC and SHAM did not change blood lactate concentration (P = 0.20) and perceived effort (P = 0.22). IPC enhanced repeated sprint swimming performance in university swimmers, whereas a placebo intervention did not.

Recent studies have reported ischemic preconditioning (IPC) can acutely improve endurance exercise performance in athletes. However, placebo and nocebo effects have not been sufficiently controlled, and the effect on aerobic metabolism parameters that determine endurance performance (e.g., oxygen cost of running, lactate threshold, and maximal oxygen uptake [V˙O2max]) has been equivocal. Thus, we circumvented limitations from previous studies to test the effect of IPC on aerobic metabolism parameters and endurance performance in well-trained runners. Eighteen runners (14 men/4 women) were submitted to three interventions, in random order: IPC; sham intervention (SHAM); and resting control (CT). Subjects were told both IPC and SHAM would improve performance compared to CT (i.e., similar placebo induction), and IPC would be harmless despite circulatory occlusion sensations (i.e., nocebo avoidance). Next, pulmonary ventilation and gas exchange, blood lactate concentration, and perceived effort were measured during a discontinuous incremental test on a treadmill. Then, a supramaximal test was used to verify the V˙O2max and assess endurance performance (i.e., time to exhaustion). Ventilation, oxygen uptake, carbon dioxide output, lactate concentration, and perceived effort were similar among IPC, SHAM, and CT throughout the discontinuous incremental test (P > 0.05). Oxygen cost of running, lactate threshold, and V˙O2max were also similar among interventions (P > 0.05). Time to exhaustion was longer after IPC (mean ± SEM, 165.34 ± 12.34 s) and SHAM (164.38 ± 11.71 s) than CT (143.98 ± 12.09 s; P = 0.02 and 0.03, respectively), but similar between IPC and SHAM (P = 1.00). IPC did not change aerobic metabolism parameters, whereas improved endurance performance. The IPC improvement, however, did not surpass the effect of a placebo intervention.

The incidence of Parkinson’s disease (PD) is increasing worldwide. Although the PD hallmark is the motor impairments, nonmotor dysfunctions are now becoming more recognized. Recently, studies have suggested that baroreflex dysfunction is one of the underlying mechanisms of cardiovascular dysregulation observed in patients with PD. However, the large body of literature on baroreflex function in PD is unclear. The baroreflex system plays a major role in the autonomic, and ultimately blood pressure and heart rate, adjustments that accompany acute cardiovascular stressors on a daily basis. Therefore, impaired baroreflex function (i.e., decreased sensitivity or gain) can lead to altered neural cardiovascular responses. Since PD affects parasympathetic and sympathetic branches of the autonomic nervous system and both are orchestrated by the baroreflex system, understanding of this crucial mechanism in PD is necessary. In the present review, we summarize the potential altered central and peripheral mechanisms affecting the feedback-controlled loops that comprise the reflex arc in patients with PD. Major factors including arterial stiffness, reduced number of C1 and activation of non-C1 neurons, presence of central α-synuclein aggregation, cardiac sympathetic denervation, attenuated muscle sympathetic nerve activity, and lower norepinephrine release could compromise baroreflex function in PD. Results from patients with PD and from animal models of PD provide the reader with a clearer picture of baroreflex function in this clinical condition. By doing so, our intent is to stimulate future studies to evaluate several unanswered questions in this research area.

Patients with Parkinson’s disease (PD) exhibit attenuated cardiovascular responses to exercise. The underlying mechanisms that are potentially contributing to these impairments are not fully understood. Therefore, we sought to test the hypothesis that patients with PD exhibit blunted cardiovascular responses to isolated muscle metaboreflex activation following exercise. For this, mean blood pressure, cardiac output, and total peripheral resistance were measured using finger photoplethysmography and the Modelflow method in 11 patients with PD [66 ± 2 yr; Hoehn and Yahr score: 2 ± 1 a.u.; time since diagnosis: 7 ± 1 yr; means ± SD) and 9 age-matched controls (66 ± 3 yr). Measurements were obtained at rest, during isometric handgrip exercise performed at 40% maximal voluntary contraction, and during postexercise ischemia. Also, a cold pressor test was assessed to confirm that blunted cardiovascular responses were specific to exercise and not representative of generalized sympathetic responsiveness. Changes in mean blood pressure were attenuated in patients with PD during handgrip (PD: ∆25 ± 2 mmHg vs. controls: ∆31 ± 3 mmHg; P < 0.05), and these group differences remained during postexercise ischemia (∆17 ± 1 mmHg vs. ∆26 ± 1 mmHg, respectively; P < 0.01). Additionally, changes in total peripheral resistance were attenuated during exercise and postexercise ischemia, indicating blunted reflex vasoconstriction in patients with PD. Responses to cold pressor test did not differ between groups, suggesting no group differences in generalized sympathetic responsiveness. Our results support the concept that attenuated cardiovascular responses to exercise observed in patients with PD are, at least in part, explained by an altered skeletal muscle metaboreflex. NEW & NOTEWORTHY Patients with Parkinson’s disease (PD) presented blunted cardiovascular responses to exercise. We showed that cardiovascular response evoked by the metabolic component of the exercise pressor reflex is blunted in patients with PD. Furthermore, patients with PD presented similar pressor response during the cold pressor test compared with age-matched controls. Altogether, our results support the hypothesis that attenuated cardiovascular responses to exercise observed in patients with PD are mediate by an altered skeletal muscle metaboreflex.

The incidence of Parkinson’s disease is increasing worldwide. The motor dysfunctions are the hallmark of the disease, but patients also experience non-motor impairments, and over 40% of the patients experience coexistent abnormalities, such as orthostatic hypotension. Exercise training has been suggested as a coping resource to alleviate Parkinson’s disease symptoms and delay disease progression. However, the body of knowledge is showing that the cardiovascular response to exercise in patients with Parkinson’s disease is altered. Adequate cardiovascular and hemodynamic adjustments to exercise are necessary to meet the metabolic demands of working skeletal muscle properly. Therefore, since Parkinson’s disease affects parasympathetic and sympathetic branches of the autonomic nervous system and the latter are crucial in ensuring these adjustments are adequately made, the understanding of these responses during exercise in this population is necessary. Several neural control mechanisms are responsible for the autonomic changes in the cardiovascular and hemodynamic systems seen during exercise. In this sense, the purpose of the present work is to review the current knowledge regarding the cardiovascular responses to dynamic and isometric/resistance exercise as well as the mechanisms by which the body maintains appropriate perfusion pressure to all organs during exercise in patients with Parkinson’s disease. Results from patients with Parkinson’s disease and animal models of Parkinson’s disease provide the reader with a well-rounded knowledge base. Through this, we will highlight what is known and not known about how the neural control of circulation is responding during exercise and the adaptations that occur when individuals exercise regularly.