Gilbert Moralez

Effect of centrally acting angiotensin converting enzyme inhibitor on the exercise‐induced increases in muscle sympathetic nerve activity

The arterial baroreflexs operating point pressure is reset upwards and rightwards from rest in direct relation to the increases in dynamic exercise intensity. The intraneural pathways and signalling mechanisms that lead to upwards and rightwards resetting of the operating point pressure, and hence the increases in central sympathetic outflow during exercise, remain to be identified. We tested the hypothesis that the central production of angiotensin II during dynamic exercise mediates the increases in sympathetic outflow and, therefore, the arterial baroreflex operating point pressure resetting during acute and prolonged dynamic exercise. The results identify that perindopril, a centrally acting angiotensin converting enzyme inhibitor, markedly attenuates the central sympathetic outflow during acute and prolonged dynamic exercise.

Losartan reduces the immediate and sustained increases in muscle sympathetic nerve activity after hyperacute intermittent hypoxia

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 1) SNA discharge and 2) 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 P < 0.01) and MAP (baseline: 89.2 ± 3.3, IHT: 92.62 ± 3.1, post-IHT: 93.83 ± 3.1 mmHg, all P < 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 P < 0.001) and MAP (baseline: 81.9 ± 2.6, IHT: 81.1 ± 2.8, post-IHT: 81.3 ± 3.0 mmHg, all P > 0.70). This investigation confirms the role of angiotensin II type 1a receptors in the immediate and persistent sympathoexcitatory and pressor responses to IHT.NEW & NOTEWORTHY 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.

Effect of increases in cardiac contractility on cerebral blood flow in humans

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-1·min-1) and then a high dose (15 μg·kg-1·min-1)] 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.NEW & NOTEWORTHY 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.

Folic acid ingestion improves skeletal muscle blood flow during graded handgrip and plantar flexion exercise in aged humans

Skeletal muscle blood flow is attenuated in aged humans performing dynamic exercise, which is due, in part, to impaired local vasodilatory mechanisms. Recent evidence suggests that folic acid improves cutaneous vasodilation during localized and whole body heating through nitric oxide-dependent mechanisms. However, it is unclear whether folic acid improves vasodilation in other vascular beds during conditions of increased metabolism (i.e., exercise). The purpose of this study was to test the hypothesis that folic acid ingestion improves skeletal muscle blood flow in aged adults performing graded handgrip and plantar flexion exercise via increased vascular conductance. Nine healthy, aged adults (two men and seven women; age: 68 ± 5 yr) performed graded handgrip and plantar flexion exercise before (control), 2 h after (acute, 5 mg), and after 6 wk (chronic, 5 mg/day) folic acid ingestion. Forearm (brachial artery) and leg (superficial femoral artery) blood velocity and diameter were measured via Duplex ultrasonography and used to calculate blood flow. Acute and chronic folic acid ingestion increased serum folate (both P < 0.05 vs. control). During handgrip exercise, acute and chronic folic acid ingestion increased forearm blood flow (both conditions P < 0.05 vs. control) and vascular conductance (both P < 0.05 vs. control). During plantar flexion exercise, acute and chronic folic acid ingestion increased leg blood flow (both P < 0.05 vs. control), but only acute folic acid ingestion increased vascular conductance (P < 0.05 vs. control). Taken together, folic acid ingestion increases blood flow to active skeletal muscle primarily via improved local vasodilation in aged adults.NEW & NOTEWORTHY Our findings demonstrate that folic acid ingestion improves blood flow via enhanced vascular conductance in the exercising skeletal muscle of aged humans. These findings provide evidence for the therapeutic use of folic acid to improve skeletal muscle blood flow, and perhaps exercise and functional capacity, in human primary aging.Listen to this articles corresponding podcast at http://ajpheart.podbean.com/e/folic-acid-and-exercise-hyperemia-in-aging/.

Tolerance to a haemorrhagic challenge during heat stress is improved with inspiratory resistance breathing

What is the central question of this study? Does inspiratory resistance breathing improve tolerance to simulated haemorrhage in individuals with elevated internal temperatures? What is the main finding and its importance? The main finding of this study is that inspiratory resistance breathing modestly improves tolerance to a simulated progressive haemorrhagic challenge during heat stress. These findings demonstrate a scenario in which exploitation of the respiratory pump can ameliorate serious conditions related to systemic hypotension.

Vasodilator Function is Impaired in Burn Injury Survivors

The effect of severe burn injury on vascular health is unknown. We tested the hypothesis that, compared with nonburn control subjects, vasodilator function would be reduced and that pulse-wave velocity (a measure of arterial stiffness) would be increased in individuals with prior burn injuries, the extent of which would be associated with the magnitude of body surface area having sustained a severe burn. Pulse-wave velocity and macrovascular (flow-mediated dilation) and microvascular (reactive hyperemia) dilator functions were assessed in 14 nonburned control subjects and 32 age-matched subjects with well-healed burn injuries. Fifteen subjects with burn injuries covering 17-40% of body surface area were assigned to a moderate burn injury group, and 17 subjects with burn injuries covering >40% of body surface area were assigned to a high burn injury group. Pulse-wave velocity [ P = 0.3 (central) and P = 0.3 (peripheral)] did not differ between the three groups. Macrovascular dilator function was reduced in the moderate ( P = 0.07) and high ( P < 0.05) burn injury groups compared with the control group. Likewise, peak vascular conductance during postocclusive reactive hyperemia differed from the moderate burn injury group ( P = 0.08 vs. control) and the high burn injury group ( P < 0.05 vs. control). These data suggest that vasodilator function is impaired in well-healed burn injury survivors, with the extent of impairment not dependent on the magnitude of body surface area having sustained a severe burn injury.