Neural Control Of Blood Pressure Research Articles

Effect of acute heat exposure on the pressor response to a voluntary hypoxic apnea.

The pressor response induced by a voluntary hypoxic apnea is mediated largely by increased sympathetic outflow. The neural control of blood pressure is altered in recovery from acute heat exposure, but its effect on the pressor response to a voluntary hypoxic apnea has never been explored. Therefore, we tested the hypothesis that prior heat exposure would attenuate the pressor response induced by a voluntary hypoxic apnea. Eleven healthy adults (five women) were exposed to whole body passive heating (water-perfused suit) sufficient to increase body core temperature by 1.2°C. Voluntary hypoxic apneas were performed at baseline and in recovery when body core temperature returned to ≤ 0.3°C of baseline. Participants breathed gas mixtures of varying [Formula: see text] (21%, 16%, and 12%; randomized) for 1 min followed by a 15-s end-expiratory apnea. The change in arterial oxygen saturation during each apnea did not differ from baseline to recovery (P = 0.6 for interaction), whereas the pressor response induced by a voluntary hypoxia apnea was reduced ([Formula: see text] 21%, baseline 17 ± 7 mmHg vs. recovery 14 ± 7 mmHg; [Formula: see text] 16%, baseline 24 ± 8 mmHg vs. recovery 18 ± 7 mmHg; [Formula: see text] 12%, baseline 28 ± 11 mmHg vs. recovery 24 ± 11 mmHg; P = 0.01 for main effect of time). These data suggest that prior heat exposure induces a cross-stressor effect such that the pressor response to a voluntary hypoxic apnea is attenuated.NEW & NOTEWORTHY The pressor response induced by a voluntary hypoxic apnea is mediated by increased sympathetic outflow. The neural control of blood pressure is altered in recovery from acute heat exposure, but its effect on the pressor response to a voluntary hypoxic apnea has never been explored. Our data suggest that prior heat exposure induces a cross-stressor effect such that the pressor response to a voluntary hypoxic apnea is attenuated.

Effect of Acute Heat Exposure on the Pressor Response to a Voluntary Hypoxic Apnea: A Cross‐Tolerance Study

The pressor response induced by a voluntary hypoxic apnea is exaggerated in individuals with obstructive sleep apnea and is strongly correlated to sympathetic overactivity. Acute heat exposure alters neural control of blood pressure, but its effect on the pressor response to a voluntary hypoxic apnea has never been explored. Therefore, we tested the hypothesis that acute heat exposure would attenuate the pressor response to a voluntary hypoxic apnea, and thereby manifest as a form of physiological cross‐tolerance. Six young adults (2 females, 25 ± 1 yrs) were exposed to passive heat stress (water‐perfused suit) sufficient to increase body core temperature by 1.2 °C. Voluntary hypoxic apneas were performed in duplicate before acute heat exposure (pre‐heat) and in recovery when body core temperature returned to ≤ 0.3 °C of baseline. Participants breathed gas mixtures of varying FiO2 (21%, 16%, and 12%; randomized) for 1 min followed immediately by a 15 s end‐expiratory apnea. Beat‐by‐beat arterial blood pressure (Finometer) and arterial oxygen saturation (finger pulse oximetry) were measured throughout. The pressor response was calculated as the difference between baseline mean arterial pressure and the peak response following each apnea. The change in arterial oxygen saturation during each apnea did not differ from pre‐heat to recovery (FiO2 21%: pre‐heat, Δ0 ± 1 % vs. recovery, Δ1 ± 2 %; FiO2 16%: pre‐heat, Δ‐4 ± 1 % vs. recovery, Δ‐3 ± 1 %; FiO2 12%: pre‐heat, Δ‐9 ± 3 % vs. recovery, Δ‐10 ± 4 %; P = 0.6 for interaction). The pressor response to a voluntary apnea was attenuated in recovery from acute heat exposure across all gas mixtures (FiO2 21%: pre‐heat, Δ14 ± 11 mmHg vs. recovery, Δ10 ± 7 mmHg; FiO2 16%: pre‐heat, Δ22 ± 15 mmHg vs. recovery, Δ15 ± 11 mmHg; FiO2 12%: pre‐heat, Δ28 ± 15 mmHg vs. recovery, Δ21 ± 16 mmHg; P < 0.01 for main effect of time). These data suggest that acute heat exposure induces a cross‐tolerance effect such that the pressor response to a voluntary hypoxic apnea is reduced. Acute heat exposure could improve hypertension in adults with obstructive sleep apnea, secondary to altered chemoreflex function and sympathetic neural control, and provide additional therapeutic options for this population to improve cardiovascular health.

Impact of sex and age on metabolism, sympathetic activity, and hypertension.

In this brief review, we summarize the current knowledge on the complex interplay between metabolism, sympathetic activity and hypertension with a focus on sex differences and changes with age in humans. Evidence suggests that in premenopausal women, sex hormones, particularly estrogen exerts a profound cardioprotective effect which may be associated with favorable metabolic profiles, as well as lower sympathetic activity and blood pressure at rest and any given physiological and environmental stimuli compared with men of a similar age. Along this line, premenopausal women seem to be generally protected from obesity-induced metabolic and cardiovascular complications. However, postmenopausal estrogen deprivation during midlife and older age has a detrimental impact on metabolism, may lead to adipose tissue redistribution from the subcutaneous to abdominal area, and augments sympathetic activity. All these changes could contribute significantly to the higher prevalence of hypertension and greater cardiometabolic risk in older women than older men. It is proposed that obesity-related hypertension has a neurogenic component which is characterized by sympathetic overactivity, but the impact of sex and age remains largely unknown. Understanding sex and age-specific differences in obesity and sympathetic neural control of blood pressure is important in the prevention and/or risk reduction of cardiometabolic disorders for both men and women.

Neural control of blood pressure during pregnancy in humans.

Previous microneurographic studies found that muscle sympathetic nerve activity (MSNA) increased in normotensive pregnant women and was even greater in women with gestational hypertension and preeclampsia during the third trimester. It is possible that sympathetic activation during the latter months of normal pregnancy helps return arterial pressure to non-pregnant levels. However, when the increase in sympathetic activity is excessive, hypertension ensues. The key question that must be addressed is whether sympathetic activation develops early during pregnancy and remains high throughout gestation, or whether this sympathetic overactivity only occurs at term, providing the substrate for preeclampsia and other pregnancy-associated cardiovascular complications. This was a literature review of autonomic neural control during pregnancy. Recent work from our laboratory and other laboratories showed that in healthy women resting MSNA increased in early pregnancy, increased further in late pregnancy, and returned to the pre-pregnancy levels shortly after delivery. We found that women who exhibited excessive sympathetic activation during the first trimester, before any clinical signs and symptoms appeared, developed gestational hypertension at term. We also found that the level of corin, an atrial natriuretic peptide-converting enzyme, was increased in the maternal circulation, especially during late pregnancy, as a homeostatic response to elevated sympathetic activity. These findings provide important insight into the neural mechanisms underlying hypertensive disorders during pregnancy. With this knowledge, early prevention or treatment targeted to the appropriate pathophysiology may be initiated, which may reduce maternal and fetal death or morbidity, as well as cardiovascular risks in women later in life.

Broader adaptive range of sympathetic burst size in response to blood pressure change in older women with greater arterial stiffness.

In this study, we focused on muscle sympathetic nerve activity (MSNA) burst size and occurrence separately as subcomponents of the sympathetic baroreflex in older adults, and we found that the distribution (variation) of burst size against burst occurrence was greater in women than men. Older women had greater carotid artery stiffness compared with older men, while blood pressure (BP) distribution (variation) was comparable between sexes. Sympathetic baroreflex sensitivity assessed with burst incidence was less sensitive as the carotid artery became stiffer in older men and women, while that assessed with burst area was more sensitive as the carotid artery became stiffer in older women but not in older men. These results help us understand the mechanisms underlying the compensation for the impaired response of MSNA burst occurrence in older women with greater carotid artery stiffness to regulate BP similar to that in older men. There are sex differences in arterial stiffness and neural control of blood pressure (BP) among older adults. We examined whether the sympathetic response to BP is greater in older women than men in burst size but not burst occurrence. Burst occurrence and size were assessed with burst interval and area of muscle sympathetic nerve activity, respectively, and the distributions of these indices were evaluated by range during supine rest in 61 healthy older subjects (30 men (69±6years) and 31 women (68±6years); means±SD). Also, we analysed sympathetic baroreflex sensitivity (BRS) with burst occurrence and area simultaneously. Carotid β-stiffness was measured with B-mode ultrasonic image and carotid BP. The range of burst interval was smaller in older women than men (P=0.002), while there was no difference in the range of burst area. Carotid β-stiffness was greater in older women than men (6.7±2.7 vs. 5.1±2.7, P=0.027). Sympathetic BRS assessed with burst incidence was lower in older women than men (-2.3±1.4 vs. -3.3±1.4 bursts·100beats-1 mmHg-1 , P=0.007), while this sex difference was observed when assessed with burst area after adjusting for carotid β-stiffness (-116.1±135.0 vs. -185.9±148.2a.u. burst-1 mmHg-1 , P=0.040), but not before. Sympathetic BRS assessed with burst area was negatively (more sensitive) correlated with carotid β-stiffness in older women (r=-0.53, P=0.002) but not men. These data suggest that the response of burst size within each burst is augmented for the baroreflex BP control despite the impaired response of burst occurrence in older women with greater carotid stiffness.

Arterial Baroreflex Function in Patients with Parkinson’s Disease: a Pharmacological Approach

Parkinson’s disease (PD) is a neurodegenerative disorder that is known for its motor dysfunction. Moreover, PD also causes non‐motor impairments, and approximately 40% of the patients experience coexistent abnormalities, like orthostatic hypotension (OH). The OH induces incapacitating symptoms that can contribute to an increased risk of falls, which have a great impact on patients’ quality of life. The arterial baroreflex system plays a pivotal role in counteracting transient falls in blood pressure during the execution of activities of daily living. Although a plethora of studies have indicated that an impaired baroreflex function is a clinical feature in patients with PD, none of the human studies have used the modified oxford method, which is considered the gold standard approach for assessing arterial baroreflex sensitivity (BRS). Additionally, since the OH and arterial BRS have an age‐dependent effect, studies with younger patients with PD is lacking. In this sense, the aim of the present study was to test the arterial baroreflex function in patients with PD with and without OH and aged‐matched control during rapid changes in blood pressure induced by sequential boluses of vasoactive drugs (Modified‐Oxford Technique). Beat‐to‐beat HR (electrocardiography) and BP (finger photoplethysmography) were obtained during 10‐min of supine rest preceding a modified‐Oxford [bolus injection of 65–100μg sodium nitroprusside (NTP) followed by 65–100μg phenylephrine hydrochloride (PHE) 1 min afterwards] in five patients with PD (50±6yr; Hohen and Yhar: <3a.u.; diagnose time: 8.8±3.7yr) and seven age‐matched controls (48±7yr). Arterial BRS was analyzed using the slopes of the linear portions of the R‐R interval‐systolic BP relationship. Patients with PD had lower BP at rest compared to controls (82±7 vs. 94±5mmHg, P=0.01) and a trend for higher HR (72±13 vs. 59±8bpm, P=0.06). The average of falling (ΔSBP: −37±0.65 vs. −31±0.43, P=0.26) and rising systolic BP (ΔSBP: −27±0.76 vs. −20±0.58, P=0.38) was similar between patients with PD and controls. Our preliminary results showed that arterial BRS was lower in patients with PD compared to controls for falling pressure (NTP trial: 4.52±0.34 vs. 9.81±0.23ms/mmHg, P=0.01) and for rising pressure (PHE trial: 5.08±0.27 vs. 13.60±0.55ms/mmHg, P=0.03). Of note, only one of the patients presented OH, and the baroreflex function was characterized by a marked blunted arterial BRS for failing pressure (NTP trial: 1.83ms/mmHg) and an averaged BRS for rising in pressure. Our preliminary results indicated that the ups and downs of baroreflex function are impaired in patients with PD, and the downs appear to be further impaired in patients with OH. These findings provide a better understanding of the neural control of blood pressure in patients with PD, and future studies should focus on OH.Support or Funding InformationCNPq, FAPDF and CAPES.

Oral Contraceptives Do Not Alter Sympathetic Neural Control of Blood Pressure in Young, Healthy Women

BackgroundSympathetic nerve activity and its effect on blood pressure are altered by female sex hormones; however, this effect differs between exogenous and endogenous hormones. With oral contraceptive (OC) use, cross‐sectional data has demonstrated higher blood pressure (BP) with no corresponding change in muscle sympathetic nerve activity (MSNA). This results in a higher BP/MSNA ratio with OC use although contributing mechanisms are unclear. The higher BP/MSNA ratio in women on OC suggests OC use may limit the ability of sympathetic baroreflex (sBRS) to suppress MSNA. Alternatively, a “burst” of MSNA could result in a greater change in BP (augmented neurovascular transduction).ObjectiveThe goal of this study was to determine if OCs alter blood pressure control through autonomic mechanisms in young women.HypothesesWe hypothesized (1) sympathetic baroreflex sensitivity would be decreased and (2) neurovascular transduction would be augmented in women on OCs compared to naturally cycling women.MethodsWe conducted a retrospective analysis of data from healthy young women taking OCs (n=30, 25±4yrs) and with natural menstrual cycles (n=23, 27±4yrs). Women were studied during the placebo phase of OC use or early follicular phase of the menstrual cycle. Heart rate (HR, 3‐lead ECG), BP (arterial line or photoplethysmography for both groups), and MSNA (peroneal nerve microneurography) were measured over 5 min of quiet rest and data were analyzed for measures of sBRS and neurovascular transduction (Ensemble, Elucimed Inc., Dunedin, New Zealand).ResultsGroups did not differ in mean BP (Control: 94±9, OC:92±8mmHg, p=0.60), or HR (Control: 61±8, OC: 62±9 bpm, p=0.57), but women on OCs had lower MSNA than controls (Control: 16±6, OC: 12±5 bursts/min, p=0.006). There were no significant differences in TPR (Control: 0.022±0.005, OC: 0.020±0.005 mmHg min/L, p=0.12), however there was a trend toward increased cardiac output in women on OCs (Control: 4.45±0.86, OC: 4.94±1.02 L/min, p=.068). There were no significant group differences in sBRS (Control: −4.3±2.1, OC: −4.0±2.6 bursts ·100 heartbeats−1 ·mmHg−1, p=0.79), or neurovascular transduction (Control: 0.093±0.042, OC: 0.091±0.058 ΔmmHg/% burst area, p=0.87). Furthermore, there were no significant correlations between BP and BRS, MSNA, or transduction in either group.ConclusionsOur data strengthen previous findings which have shown women taking OCs have higher BP for a given MSNA. The analysis we performed build on these results and demonstrate that the increase in BP for a given MSNA in women taking OCs is not due to attenuated sBRS or augmented neurovascular transduction. This work has advanced our understanding of the alteration of blood pressure with OC use in young women.Support or Funding InformationNIH HL083947

Neural control of blood pressure is altered following isolated leg heating in aged humans

There is a sustained reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating. We tested the hypothesis that acute leg heating would decrease arterial blood pressure in aged adults secondary to sympathoinhibition. We exposed 13 young and 10 aged adults to 45 min of leg heating. Muscle sympathetic nerve activity (radial nerve) was measured before leg heating (preheat) and 30 min after (recovery) and is expressed as burst frequency. Neurovascular transduction was examined by assessing the slope of the relation between muscle sympathetic nerve activity and leg vascular conductance measured at rest and during isometric handgrip exercise performed to fatigue. Arterial blood pressure was well maintained in young adults (preheat, 86 ± 6 mmHg vs. recovery, 88 ± 7 mmHg; P = 0.4) due to increased sympathetic nerve activity (preheat, 16 ± 7 bursts/min vs. recovery, 22 ± 10 bursts/min; P < 0.01). However, in aged adults, sympathetic nerve activity did not differ from preheat (37 ± 5 bursts/min) to recovery (33 ± 6 bursts/min, P = 0.1), despite a marked reduction in arterial blood pressure (preheat, 101 ± 7 mmHg vs. recovery, 94 ± 6 mmHg; P < 0.01). Neurovascular transduction did not differ from preheat to recovery for either age group (P ≥ 0.1). The reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating is mediated, in part, by a sympathoinhibitory effect that alters the compensatory neural response to hypotension.NEW & NOTEWORTHY There is a sustained reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating. However, the neurovascular mechanisms mediating this response remain unknown. Our findings demonstrate for the first time that this reduction in arterial blood pressure is mediated, in part, by a sympathoinhibitory effect that alters the compensatory neural response to hypotension in aged adults.

(Pro)renin receptor knockdown in the paraventricular nucleus of the hypothalamus attenuates hypertension development and AT1 receptor-mediated calcium events.

Activation of the brain renin-angiotensin system (RAS) is a pivotal step in the pathogenesis of hypertension. The paraventricular nucleus (PVN) of the hypothalamus is a critical part of the angiotensinergic sympatho-excitatory neuronal network involved in neural control of blood pressure and hypertension. However, the importance of the PVN (pro)renin receptor (PVN-PRR)-a key component of the brain RAS-in hypertension development has not been examined. In this study, we investigated the involvement and mechanisms of the PVN-PRR in DOCA-salt-induced hypertension, a mouse model of hypertension. Using nanoinjection of adeno-associated virus-mediated Cre recombinase expression to knock down the PRR specifically in the PVN, we report here that PVN-PRR knockdown attenuated the enhanced blood pressure and sympathetic tone associated with hypertension. Mechanistically, we found that PVN-PRR knockdown was associated with reduced activation of ERK (extracellular signal-regulated kinase)-1/2 in the PVN and rostral ventrolateral medulla during hypertension. In addition, using the genetically encoded Ca2+ biosensor GCaMP6 to monitor Ca2+-signaling events in the neurons of PVN brain slices, we identified a reduction in angiotensin II type 1 receptor-mediated Ca2+ activity as part of the mechanism by which PVN-PRR knockdown attenuates hypertension. Our study demonstrates an essential role of the PRR in PVN neurons in hypertension through regulation of ERK1/2 activation and angiotensin II type 1 receptor-mediated Ca2+ activity. NEW & NOTEWORTHY PRR knockdown in PVN neurons attenuates the development of DOCA-salt hypertension and autonomic dysfunction through a decrease in ERK1/2 activation in the PVN and RVLM during hypertension. In addition, PRR knockdown reduced AT1aR expression and AT1R-mediated calcium activity during hypertension. Furthermore, we characterized the neuronal targeting specificity of AAV serotype 2 in the mouse PVN and validated the advantages of the genetically encoded calcium biosensor GCaMP6 in visualizing neuronal calcium activity in the PVN.

Anti-Hypertensive Action of Fenofibrate via UCP2 Upregulation Mediated by PPAR Activation in Baroreflex Afferent Pathway.

Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha (PPAR-α), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-α and PPAR-γ was assessed in the nodose ganglion (NG) and the nucleus of the solitary tract (NTS). Hypertension induced by drinking high fructose (HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-α and PPAR-γ were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-α, the mitochondrial uncoupling protein 2 (UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats. These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.

Neural Control of Blood Pressure and Body Temperature During Heat Stress

Abstract Environmental heat stress is associated with a marked decrease in orthostatic tolerance (OT), which is defined as the ability to stand or sit upright without symptoms of dizziness, lighthe...

Neural Programmatic Role of Leptin, TNFα, Melanocortin, and Glutamate in Blood Pressure Regulation vs Obesity-Related Hypertension in Male C57BL/6 Mice.

Continuous nutritional surplus sets the stage for hypertension development. Whereas moderate dietary obesity in mice is normotensive, the homeostatic balance is disrupted concurrent with an increased risk of hypertension. However, it remains unclear how the obesity-associated prehypertensive state is converted into overt hypertension. Here, using mice with high-fat-diet (HFD)-induced moderate obesity vs control diet (CD)-fed lean mice, we comparatively studied the effects of central leptin and tumor necrosis factor-α (TNFα) as well as the involvement of the neuropeptide melanocortin pathway vs the neurotransmitter glutamate pathway. Compared with CD-fed lean mice, the pressor effect of central excess leptin and TNFα, but not melanocortin, was sensitized in HFD-fed mice. The pressor effect of central leptin in HFD-fed mice was strongly suppressed by glutamatergic inhibition but not by melanocortinergic inhibition. The pressor effect of central TNFα was substantially reversed by melanocortinergic inhibition in HFD-fed mice but barely in CD-fed mice. Regardless of diet, the hypertensive effects of central TNFα and melanocortin were both partially reversed by glutamatergic suppression. Hence, neural control of blood pressure is mediated by a signaling network between leptin, TNFα, melanocortin, and glutamate and changes in dynamics due to central excess leptin and TNFα mediate the switch from normal physiology to obesity-related hypertension.

Neural control of blood pressure in women: differences according to age.

The blood pressure "error signal" represents the difference between an individual's mean diastolic blood pressure and the diastolic blood pressure at which 50% of cardiac cycles are associated with a muscle sympathetic nerve activity burst (the "T50"). In this study we evaluated whether T50 and the error signal related to the extent of change in blood pressure during autonomic blockade in young and older women, to study potential differences in sympathetic neural mechanisms regulating blood pressure before and after menopause. We measured muscle sympathetic nerve activity and blood pressure in 12 premenopausal (25±1years) and 12 postmenopausal women (61±2years) before and during complete autonomic blockade with trimethaphan camsylate. At baseline, young women had a negative error signal (-8±1 versus 2±1mmHg, p<0.001; respectively) and lower muscle sympathetic nerve activity (15±1 versus 33±3bursts/min, p<0.001; respectively) than older women. The change in diastolic blood pressure after autonomic blockade was associated with baseline T50 in older women (r=-0.725, p=0.008) but not in young women (r=-0.337, p=0.29). Women with the most negative error signal had the lowest muscle sympathetic nerve activity in both groups (young: r=0.886, p<0.001; older: r=0.870, p<0.001). Our results suggest that there are differences in baroreflex control of muscle sympathetic nerve activity between young and older women, using the T50 and error signal analysis. This approach provides further information on autonomic control of blood pressure in women.

Low-level Chronic Lead Exposure Impairs Neural Control of Blood Pressure and Heart Rate in Rats.

Lead (Pb) induces adverse effects when it chronically accumulates in the body, including effects on the nervous and cardiovascular systems. Wistar rats were exposed to lead acetate for 30days (first dose 4µg/100g followed by 0.05µg/100g/day, i.m.) to investigate the cardiovascular system impact on the autonomic control. The femoral artery and vein were catheterised to perform hemodynamic evaluations in awake rats: heart rate variability (HRV), baroreflex sensitivity, cardiopulmonary reflex and hemodynamic responses to vagal and sympathetic pharmacological blockade. Rats exposed to Pb exhibited a higher blood pressure and reduced HRV in the time domain when compared to the saline-injected group. Spectral analysis of the HRV in the frequency-domain showed an augmented low-frequency component of the spectrum. Methylatropine and atenolol administration suggest increased sympathetic tone and reduced vagal tone on the control of heart rate. Chronic Pb exposure decreased the sensitivity of the baroreflex without significantly changing the cardiopulmonary reflex. This study demonstrated for the first time in an animal model of a controlled, low-dose chronic lead exposure that cardiovascular changes, such as arterial hypertension, are accompanied by impaired autonomic control of the cardiovascular system, as characterised by reduced baroreflex sensitivity and a sympathovagal imbalance.

Exaggerated haemodynamic and neural responses to involuntary contractions induced by whole-body vibration in normotensive obese versus lean women.

What is the central question of this study? In obesity, the exaggerated blood pressure response to voluntary exercise is linked to hypertension, yet the mechanisms are not fully elucidated. We examined whether involuntary contractions elicit greater haemodynamic responses and altered neural control of blood pressure in normotensive obese versus lean women. What is the main finding and its importance? During involuntary contractions induced by whole-body vibration, there were augmented blood pressure and spontaneous baroreflex responses in obese compared with lean women. This finding is suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity. Passive contractions did not elicit differential heart rate responses in obese compared with lean women, implying other mechanisms for the blunted heart rate response reported during voluntary exercise in obesity. In obesity, the exaggerated blood pressure (BP) response to exercise is linked to hypertension, yet the mechanisms are not fully elucidated. In this study, we examined whether involuntary mechanical oscillations, induced by whole-body vibration (WBV), elicit greater haemodynamic responses and altered neural control of BP in obese versus lean women. Twenty-two normotensive, premenopausal women (12 lean and 10 obese) randomly underwent a passive WBV (25Hz) and a control protocol (similar posture without WVB). Beat-by-beat BP, heart rate, stroke volume, systemic vascular resistance, cardiac output, parasympathetic output (evaluated by heart rate variability) and spontaneous baroreceptor sensitivity (sBRS) were assessed. We found that during WBV, obese women exhibited an augmented systolic BP response compared with lean women that was correlated with body fat percentage (r = 0.77; P<0.05). The exaggerated BP rise was driven mainly by the greater increase in cardiac output index in obese versus lean women, associated with a greater stroke volume index in obese women. Involuntary contractions did not elicit a differential magnitude of responses in heart rate, heart rate variability indices and systemic vascular resistance in obese versus lean women; however, they did result in greater sBRS responses (P<0.05) in obese women. In conclusion, involuntary contractions elicited an augmented BP and sBRS response in normotensive obese versus lean women. The greater elevations in circulatory haemodynamics in obese women are suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity.

Neural Control of Blood Pressure in Chronic Intermittent Hypoxia.

Sleep apnea (SA) is increasing in prevalence and is commonly comorbid with hypertension. Chronic intermittent hypoxia is used to model the arterial hypoxemia seen in SA, and through this paradigm, the mechanisms that underlie SA-induced hypertension are becoming clear. Cyclic hypoxic exposure during sleep chronically stimulates the carotid chemoreflexes, inducing sensory long-term facilitation, and drives sympathetic outflow from the hindbrain. The elevated sympathetic tone drives hypertension and renal sympathetic activity to the kidneys resulting in increased plasma renin activity and eventually angiotensin II (Ang II) peripherally. Upon waking, when respiration is normalized, the sympathetic activity does not diminish. This is partially because of adaptations leading to overactivation of the hindbrain regions controlling sympathetic outflow such as the nucleus tractus solitarius (NTS), and rostral ventrolateral medulla (RVLM). The sustained sympathetic activity is also due to enhanced synaptic signaling from the forebrain through the paraventricular nucleus (PVN). During the waking hours, when the chemoreceptors are not exposed to hypoxia, the forebrain circumventricular organs (CVOs) are stimulated by peripherally circulating Ang II from the elevated plasma renin activity. The CVOs and median preoptic nucleus chronically activate the PVN due to the Ang II signaling. All together, this leads to elevated nocturnal mean arterial pressure (MAP) as a response to hypoxemia, as well as inappropriately elevated diurnal MAP in response to maladaptations.

Emotional Stress as a Risk for Hypertension in Sub-Saharan Africans: Are We Ignoring the Odds?

Globally most interventions focus on improving lifestyle habits and treatment regimens to combat hypertension as a non-communicable disease (NCD). However, despite these interventions and improved medical treatments, blood pressure (BP) values are still on the rise and poorly controlled in sub-Saharan Africa (SSA). Other factors contributing to hypertension prevalence, such as chronic emotional stress, might provide some insight for future health policy approaches.Currently, Hypertension Society guidelines do not mention emotional stress as a probable cause for hypertension. Recently the 2014 World Global Health reports, suggested that African governments should consider using World Health Organization hypertension data as a proxy indicator for social well-being. However, the possibility that a stressful life and taxing environmental factors might disturb central neural control of BP regulation has largely been ignored in SSA.Linking emotional stress to vascular dysregulation is therefore one way to investigate increased cardiometabolic challenges, neurotransmitter depletion and disturbed hemodynamics. Disruption of stress response pathways and subsequent changes in lifestyle habits as ways of coping with a stressful life, and as probable cause for hypertension prevalence in SSA, may be included in future preventive measures. We will provide an overview on emotional stress and central neural control of BP and will include also implications thereof for clinical practice in SSA cohorts.

Central integration and neural control of blood pressure during the cold pressor test: a comparison between hydrochlorothiazide and aliskiren.

Individuals with hypertension and sympathetic overactivity are at risk for cardiovascular events. Renin inhibitors are new while thiazide diuretics are first-class drugs used for treatment of hypertension. The purpose of this study was to determine whether 6 months of treatment with aliskiren (ALSK) or hydrochlorothiazide (HCTZ) would alter blood pressure (BP) and muscle sympathetic nerve activity (MSNA) indices in older mild hypertensives during a cold pressor test (CPT). We hypothesized that the ALSK group would demonstrate a blunted response compared to HCTZ. Nineteen (9 men, 10 women) subjects performed a CPT pre- and post treatment where heart rate (HR), systolic BP (SBP) and diastolic BP (DBP), and MSNA were measured. Blood samples were withdrawn for assessment of renal-adrenal hormones. Both medications lowered ambulatory SBP and DBP (P < 0.05). Direct renin tended to be higher in the ALSK group after treatment (P = 0.081). Aldosterone was higher in the HCTZ group after treatment (P < 0.001). As expected, both groups showed increases in HR, SBP, DBP, and MSNA during the CPT (all P < 0.05). All cardiovascular and MSNA responses were similar pre- and post treatment in both groups (peak CPT SBP: 26 ± 10 vs. 17 ± 21 and 21 ± 20 vs. 29 ± 15 mmHg for pre vs. post for HCTZ and ALSK, respectively; peak CPT MSNA burst frequency: 13 ± 8 vs. 11 ± 11 and 11 ± 17 vs. 6 ± 13 bursts/min; all P > 0.05). Treatment with these antihypertensive medications lowered BP but was not successful in lowering the responsiveness to the CPT.

Abstract 272: Divergent Neural Control of Blood Pressure vs Resting Metabolic Rate by Angiotensin: The Role of AT 1A Signaling in Leptin-Sensitive Cells

The renin-angiotensin system (RAS) and leptin both contribute to resting metabolic rate (RMR) and blood pressure control, and thus may contribute to obesity-hypertension. Previously we demonstrated a required role for angiotensin AT 1A receptors in the brain in RMR, and renal and sympathetic nerve activity (SNA) responses to leptin. Here we tested the hypothesis that AT 1A receptors, specifically localized to leptin-sensitive cells, are required for the blood pressure and RMR effects of brain ANG. The AT 1A gene was conditionally disrupted in cells that express the long (b) form of the leptin receptor (ObRb-Cre x AT 1A flox mice; “KO”), and blood pressure was assessed by radiotelemetry under baseline and deoxycorticosterone (DOCA)-salt stimulated conditions. While 24-hr blood pressure (MAP; control n=10, 115 ± 4, vs KO n=9, 115 ± 6 mmHg) and heart rate (control n=10, 561 ± 9, vs KO 563 ± 11 BPM) were not different between control and KO mice, baroreflex sensitivity was significantly increased in KO mice at baseline (control n=6, 3.4 ± 0.7, vs KO n=6, 5.6 ± 0.5 msec/mmHg, P&lt;0.05). DOCA-salt significantly increased MAP (control=8, 130 ± 4, vs KO n=7, 129 ± 3) and decreased baroreflex sensitivity (control=6, 3.0 ± 0.5, vs KO n=5, 2.8 ± 0.5, P&lt;0.05 vs baseline) in all mice. In contrast, RMR responses to DOCA-salt were abolished in KO mice (baseline n=2, 0.2 ± 0.01, vs DOCA-salt n=2, 0.2 ± 0.02). We conclude that AT 1A signaling specifically in leptin-sensitive cells is critically involved in RMR control, but is relatively dispensable for cardiovascular control. To further characterize the cells that mediate the leptin-AT 1A interaction critical for RMR control, we performed immunohistochemical staining for adrenocorticotropin (ACTH) in the arcuate nucleus of mice that express GFP via the AT 1A promoter (“NZ44”). Complete lack of colocalization supports the conclusion that AT 1A are not expressed by proopiomelanocortin (POMC) neurons. In contrast, KO mice exhibit a baseline increase in glutamate decarboxylase mRNA in the arcuate nucleus, consistent with a possible localization of AT 1A upon agouti related peptide (AgRP) neurons. AT 1A may therefore suppress AgRP neuron γ-aminobutyric acid production and thus disinhibit POMC neuronal activity, to ultimately stimulate RMR.

Sympathetic Neural Regulation of Blood Pressure: Influences of Sex and Aging

Sex and age have important influences on sympathetic neural control of blood pressure in humans. Young women are relatively protected against risk of hypertension due to greater peripheral vasodilator influences compared with young men and older people. This protective effect is lost at menopause. Older men and women have higher sympathetic nerve activity and tighter coupling between SNA and blood pressure, contributing to the increased risk of hypertension with aging.