Rationale: Chronic exposure to hypoxia is associated with elevated sympathetic nervous activity and reduced vascular function in lowlanders, and Andean highlanders suffering from excessive erythrocytosis (EE); however, the mechanistic link between chronically elevated sympathetic nervous activity and hypoxia-induced vascular dysfunction has not been determined. Objective: To determine the impact of heightened sympathetic nervous activity on resistance artery endothelial-dependent dilation (EDD), and endothelial-independent dilation, in lowlanders and Andean highlanders with and without EE. Methods and Results: We tested healthy lowlanders (n=9) at sea level (344 m) and following 14 to 21 days at high altitude (4300 m), and permanent Andean highlanders with (n=6) and without (n=9) EE at high altitude. Vascular function was assessed using intraarterial infusions (3 progressive doses) of acetylcholine (ACh; EDD) and sodium nitroprusside (endothelial-independent dilation) before and after local α+β adrenergic receptor blockade (phentolamine and propranolol). Intraarterial blood pressure, heart rate, and simultaneous brachial artery diameter and blood velocity were recorded at rest and during drug infusion. Changes in forearm vascular conductance were calculated. The main findings were (1) chronic hypoxia reduced EDD in lowlanders (changes in forearm vascular conductance from sea level: ACh1: −52.7±19.6%, ACh2: −25.4±38.7%, ACh3: −35.1±34.7%, all P ≤0.02); and in Andeans with EE compared with non-EE (changes in forearm vascular conductance at ACh3: −36.4%, P =0.007). Adrenergic blockade fully restored EDD in lowlanders at high altitude, and normalized EDD between EE and non-EE Andeans. (2) Chronic hypoxia had no effect on endothelial-independent dilation in lowlanders, and no differences were detected between EE and non-EE Andeans; however, EID was increased in the non-EE Andeans after adrenergic blockade ( P =0.012), but this effect was not observed in the EE Andeans. Conclusions: These data indicate that chronic hypoxia reduces EDD via heightened α-adrenergic signaling in lowlanders and in Andeans with EE. These vascular mechanisms have important implications for understanding the physiological consequences of acute and chronic high altitude adaptation.

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia, which produces elevations in sympathetic nerve activity (SNA) and associated hypertension in experimental models that persist beyond the initial exposure. We tested the hypotheses that angiotensin receptor blockade in humans using losartan attenuates the immediate and immediately persistent increases in ) SNA discharge and) mean arterial pressure (MAP) after hyperacute intermittent hypoxia training (IHT) using a randomized, placebo-controlled, repeated-measures experimental design. We measured ECG and photoplethysmographic arterial pressure in nine healthy human subjects, while muscle SNA (MSNA) was recorded in seven subjects using microneurography. Subjects were exposed to a series of hypoxic apneas in which they inhaled two to three breaths of nitrogen, followed by a 20-s apnea and 40 s of room air breathing every minute for 20 min. Hyperacute IHT produced substantial and persistent elevations in MSNA burst frequency (baseline: 15.3 ± 1.8, IHT: 24 ± 1.5, post-IHT 20.0 ± 1.3 bursts/min, all < 0.01) and MAP (baseline: 89.2 ± 3.3, IHT: 92.62 ± 3.1, post-IHT: 93.83 ± 3.1 mmHg, all < 0.02). Losartan attenuated the immediate and sustained increases in MSNA (baseline: 17.3 ± 2.5, IHT: 18.6 ± 2.2, post-IHT 20.0 ± 1.3 bursts/min, all < 0.001) and MAP (baseline: 81.9 ± 2.6, IHT: 81.1 ± 2.8, post-IHT: 81.3 ± 3.0 mmHg, all > 0.70). This investigation confirms the role of angiotensin II type 1a receptors in the immediate and persistent sympathoexcitatory and pressor responses to IHT. This study demonstrates for the first time in humans that losartan, an angiotensin receptor blocker (ARB), abrogates the acute and immediately persistent increases in muscle sympathetic nerve activity and arterial pressure in response to acute intermittent hypoxia. This investigation, along with others, provides important beginning translational evidence for using ARBs in treatment of the intermittent hypoxia observed in obstructive sleep apnea patients.

The effect of acute increases in cardiac contractility on cerebral blood flow (CBF) remains unknown. We hypothesized that the external carotid artery (ECA) downstream vasculature modifies the direct influence of acute increases in heart rate and cardiac function on CBF regulation. Twelve healthy subjects received two infusions of dobutamine [first a low dose (5 μg·kg·min) and then a high dose (15 μg·kg·min)] for 12 min each. Cardiac output, blood flow through the internal carotid artery (ICA) and ECA, and echocardiographic measurements were performed during dobutamine infusions. Despite increases in cardiac contractility, cardiac output, and arterial pressure with dobutamine, ICA blood flow and conductance slightly decreased from resting baseline during both low- and high-dose infusions. In contrast, ECA blood flow and conductance increased appreciably during both low- and high-dose infusions. Greater ECA vascular conductance and corresponding increases in blood flow may protect overperfusion of intracranial cerebral arteries during enhanced cardiac contractility and associated increases in cardiac output and perfusion pressure. Importantly, these findings suggest that the acute increase of blood perfusion attributable to dobutamine administration does not cause cerebral overperfusion or an associated risk of cerebral vascular damage. A dobutamine-induced increase in cardiac contractility did not increase internal carotid artery blood flow despite an increase in cardiac output and arterial blood pressure. In contrast, external carotid artery blood flow and conductance increased. This external cerebral blood flow response may assist with protecting from overperfusion of intracranial blood flow.

Lower HRV was observed at rest following concussion. An increase in HRV, suggestive of enhanced prefrontal cortex (PFC) functioning, was observed during a cognitive task in the concussed athletes. Therefore, cognitive tasks as early as 4 days after injury may increase PFC functioning from rest and expedite return to learn in collegiate athletes.

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The present study evaluated whether wearing a water-soaked t-shirt, with or without electric fan use, mitigates thermal and cardiovascular strain in older individuals exposed to hot and moderately humid conditions. Nine healthy older individuals (68 ± 4 yr; five women) completed three 120-min heat exposures (42.4 ± 0.2°C, 34.2 ± 0.9% relative humidity) on separate days while wearing a dry t-shirt (CON), a t-shirt soaked with 500 ml of tap water (WET), or a t-shirt soaked with 500 ml of tap water while facing an electric fan (2.4 ± 0.4 m/s; WET+FAN). Measurements included core and skin temperatures, evaporative mass losses, heart rate, and blood pressure. In the WET condition, elevations in core temperature were attenuated compared with DRY from 30 to 120 min and compared with WET+FAN from 30 to 90 min ( P < 0.05). Evaporative mass losses (inclusive of sweat and water losses from the shirt) were greatest in WET+FAN, followed by WET, and then DRY ( P < 0.01). Sweat losses were lowest in WET, followed by DRY, and then WET+FAN ( P < 0.01). Heart rate was lower only at 60 min in WET versus DRY ( P = 0.01). No differences in mean arterial pressure were observed ( P = 0.51). In conclusion, wearing a water-soaked t-shirt without, but not with, electric fan use is an effective heat management strategy to mitigate thermal strain and lower sweat losses in older individuals exposed to hot and moderately humid conditions. NEW & NOTEWORTHY In older individuals exposed to hot and moderately humid environments, electric fan use coupled with a water-soaked t-shirt exacerbates sweat losses without mitigating heat strain compared with a dry t-shirt. However, wearing a water-soaked t-shirt without fan use reduces sweat losses and attenuates heat strain compared with a dry t-shirt and a fan/water-soaked t-shirt combination. These findings suggest wearing a water-soaked t-shirt is an effective heat-management strategy for older individuals during heat waves when air conditioning is inaccessible.

We tested the hypothesis that dehydration exacerbates reductions of middle cerebral artery blood velocity (MCAv) and alters cerebrovascular control during standing after heavy resistance exercise. Ten males participated in two trials under 1) euhydration (EUH) and 2) dehydration (DEH; fluid restriction + 40 mg furosemide). We recorded finger photoplethysmographic arterial pressure and MCAv (transcranial Doppler) during 10 min of standing immediately after high-intensity leg press exercise. Symptoms (e.g., lightheadedness) were ranked by subjects during standing (1-5 scale). Low-frequency (LF) oscillations of mean arterial pressure (MAP) and mean MCAv were calculated as indicators of cerebrovascular control. DEH reduced plasma volume by 11% (P = 0.002; calculated from hemoglobin and hematocrit). During the first 30 s of standing after exercise, subjects reported greater symptoms during DEH vs. EUH (P = 0.05), but these were mild and resolved at 60 s. While MAP decreased similarly between conditions immediately after standing, MCAv decreased more with DEH than EUH (P = 0.02). With prolonged standing under DEH, mean MCAv remained below baseline (P ≤ 0.01), and below EUH values (P ≤ 0.05). LF oscillations of MAP were higher for DEH at baseline and during the entire 10 min of stand after exercise (P ≤ 0.057), while LF oscillations in mean MCAv were distinguishable only at baseline and 5 min following stand (P = 0.05). Our results suggest that mean MCAv falls below a "symptomatic threshold" in the acute phase of standing after exercise during DEH, although symptoms were mild and transient. During the prolonged phase of standing, increases in LF MAP and mean MCAv oscillations with DEH may help to maintain cerebral perfusion despite absolute MCAv remaining below the symptomatic threshold.

Low dose ketamine is a leading medication used to provide analgesia in pre-hospital and hospital settings. Low dose ketamine is increasingly used off-label to treat conditions such as depression. r In animals, ketamine stimulates the sympathetic nervous system and increases blood pressure, but these physiological consequences have not been studied in conscious humans. r Our data suggest that low dose ketamine administration blunts pain perception and reduces blood pressure, but not muscle sympathetic nerve activity burst frequency, responses during a cold pressor test in healthy humans. r These mechanistic, physiological results inform risk-benefit analysis for clinicians administering low dose ketamine in humans.