Interaction of simultaneous hypoxia and baroreflex loading on control of sympathetic action potential subpopulations.

Efferent muscle sympathetic nerve activity (MSNA) is under tonic baroreflex control. The arterial baroreflex exerts the strongest influence over medium-sized sympathetic action potential (AP) subpopulations in efferent MSNA recordings. Prior work from multiunit MSNA recordings has shown baroreflex loading selectively abolishes the sympathetic response to hypoxia. The purpose of the study was to examine baroreflex control over different-sized AP clusters and characterize the neural recruitment strategies of sympathetic AP subpopulations with baroreflex and combined baroreflex/chemoreflex (i.e., hypoxia) activation. We loaded the arterial baroreceptors [intravenous phenylephrine (PE)] alone and in combination with systemic hypoxia ([Formula: see text] 80%) in nine healthy young men. We extracted sympathetic APs using the wavelet-based methodology and quantified baroreflex gain for individual AP clusters. AP baroreflex threshold gain was measured as the slope of the linear relationship between AP probability versus diastolic blood pressure for 10 normalized clusters. Baroreflex loading with phenylephrine decreased MSNA and AP firing compared with baseline (all P < 0.05). However, the phenylephrine-mediated decrease in AP firing was lost with concurrent hypoxia (P = 0.384). Compared with baseline, baroreflex loading reduced medium-sized AP cluster baroreflex threshold slope (condition P = 0.005) and discharge probability (condition P < 0.0001); these reductions from baseline were maintained during simultaneous hypoxia (both P < 0.05). Present findings indicate a key modulatory role of the baroreceptors on medium-sized APs in blood pressure regulation that withstands competing signals from peripheral chemoreflex activation.NEW & NOTEWORTHY This study provides a novel understanding on baroreflex control of efferent sympathetic nervous system activity during competing stressors: baroreflex loading and peripheral chemoreflex activation. We show chemoreflex activation buffers baroreflex-mediated reductions in sympathetic nervous system activity. More importantly, baroreflex loading reduced baroreflex threshold gain of sympathetic action potential clusters and this reduction withstood chemoreflex activation. These data suggest the arterial baroreflex holds a primary regulatory role over medium-sized sympathetic neurons despite competing chemoreflex signals.

Advancing cardiovascular neuromodulation: Aortic baroreceptor afferents act as targets for blood pressure control in hypertension.

Aortic baroreceptor afferents act as targets for blood pressure control in hypertension.

Carotid baroreceptor dysfunction after carotid body tumour resections.

OBJECTIVE: Carotid body tumours (CBTs) and baroreceptor failure (BRF) are two distinct but interrelated conditions, affecting the carotid body and its regulatory mechanisms. We aim to describe and quantify BRF after unilateral and bilateral CBT resections. METHODS: Prospective cohort study. We included all patients with unilateral or bilateral CBT undergoing resection from April 2021 to January 2023. Demographics and CBTs characteristics were analysed; baroreceptor sensitivity assessment was conducted using the Composite Autonomic Severity Score (CASS). Statistical analyses were performed using R. Significance level was set at a 2-tailed α = 0.05. RESULTS: A total of 30 patients with CBT underwent surgical resection, twenty-three were included in the study (18 unilateral and 5 bilateral CBTs). All 23 (100 %) were females, median age of 60 years. Regarding patients with unilateral CBT; preoperatively, 13 had BRF, the most common dysfunction subtype was mixed. Postoperatively, the most common dysfunction subtype was sympathetic failure. With regards to bilateral CBTs; 2 patients did not have autonomic dysfunction preoperatively. After bilateral surgical resection one patient remained without autonomic dysfunction; however, all other patients persisted with BRF. CONCLUSION: BRF was present in 13 patients with unilateral CBT and 3 patients with bilateral tumours preoperatively; most will remain with BRF and will only change the characteristics postoperatively. No associations were found between type, severity of BRF and Shamblin classification or laterality. It is paramount that research in this area continues as many features are yet unknown regarding CBT pathogenesis, hence, BRF may be present yet not affect significantly quality of life.

Independent Factors Influencing Changes in Baroreceptor Sensitivity after Carotid Endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is a well-established standard therapy for patients with symptomatic or asymptomatic high-grade carotid stenosis. The aim of carotid endarterectomy is to decrease the risk of stroke and avoid relevant functional loss. However, carotid endarterectomy is known to be associated with hemodynamic dysregulation. In this study we compared eversion CEA (E-CEA) and conventional CEA (C-CEA) regarding postoperative blood pressure values as well as preoperative and postoperative baroreceptor sensitivity in the first 7 days after surgery. The aim was to find possible factors influencing changes in baroreceptor sensitivity. METHODS: Patients (111 patients were enrolled, of which 50 patients received C-CEA and 61 patients E-CEA) were prospectively enrolled in this study. For the measurement of baroreceptor sensitivity, a noninvasive Finometer measuring device from Finapres Medical System B.V. (Amsterdam, The Netherlands) was used. Measurements were performed 1 day before surgery (PRE), directly after surgery (F1), on day 1 (F2), day 2 (F3), and on day 7 (F4) postoperatively. RESULTS: Postoperative blood pressure values were significantly higher in the E-CEA group on the day of surgery (F1) (P < 0.001) and on day 1 (F2) (P < 0.001). From day 2 (F3, F4) postoperatively, no significant difference was found between the 2 groups. The invasive blood pressure measurement in the postoperative recovery room showed significantly higher systolic blood pressure values in the E-CEA group (P = 0.001). The need of acute antihypertensive therapy was significantly higher in the recovery room in the E-CEA group (P = 0.020). With regard to changes in baroreceptor sensitivity, significantly lower baroreceptor sensitivity (BRS) values were recorded in the E-CEA group at 1 day (F2) postoperatively (P = 0.005). The regression analysis showed that the applied surgical technique and the patient's age were significant factors influencing changes in baroreceptor sensitivity. CONCLUSIONS: In this study we could confirm higher blood pressure levels after E-CEA in the first 2 days after surgery. Additionally, we identified 22 factors possibly influencing baroreceptor sensitivity: surgical technique and age. Based on the data obtained in this study, hemodynamic dysregulation after CEA (E-CEA, C-CEA) is temporary and short-term. Already after the second postoperative day, there was no significant difference between the E-CEA and E-CEA groups, this effect remained stable after 7 days.

Sympathoinhibition during cardiopulmonary baroreceptor loading is attenuated in older females.

The purpose of the present study was to clarify the impact of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. Nine older females (mean ± SD, 70 ± 6 yr) and 11 younger females (20 ± 1 yr) completed the study. A passive leg raising (PLR) test was performed wherein the participants were positioned supine (baseline, 0°), and their lower limbs were passively lifted at 10°, 20°, 30°, and 40° (3 min at each angle). Muscle sympathetic nerve activity (MSNA) was recorded via microneurography of the left radial nerve. The central venous pressure was estimated based on peripheral venous pressure (eCVP), which was monitored using a cannula in the right large antecubital vein. Baseline MSNA was higher in older females than in younger females. MSNA burst frequency (BF) decreased during the PLR test in both older and younger females, but the magnitude of the decrease in MSNA BF was smaller in older females than in younger females (older, -3.5 ± 1.5 vs. younger, -6.3 ± 1.5 bursts/min at 40° from baseline, P = 0.014). The eCVP increased during the PLR in both groups, and there was no difference in the changes in eCVP between the two groups (older, +1.07 ± 0.37 vs. younger, +1.12 ± 0.33 mmHg at 40° from baseline, P = 0.941). These results suggest that inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age in females.NEW & NOTEWORTHY There were no available data concerning the effect of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. The magnitude of the decrease in muscle sympathetic nerve activity during passive leg raising (10°-40°) was smaller in older females than in young females. In females, inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age.

Effects of acute carotid baroreceptor stimulation on sympathetic nerve traffic in resistant and uncontrolled hypertension: a systematic review and meta-analysis.

In resistant hypertensive patients acute carotid baroreflex stimulation is associated with a blood pressure (BP) reduction, believed to be mediated by a central sympathoinhbition.The evidence for this sympathomodulatory effect is limited, however. This meta-analysis is the first to examine the sympathomodulatory effects of acute carotid baroreflex stimulation in drug-resistant and uncontrolled hypertension, based on the results of microneurographic studies. The analysis included 3 studies assessing muscle sympathetic nerve activity (MSNA) and examining 41 resistant uncontrolled hypertensives. The evaluation included assessment of the relationships between MSNA and clinic heart rate and BP changes associated with the procedure. Carotid baroreflex stimulation induced an acute reduction in clinic systolic and diastolic BP which achieved statistical significance for the former variable only [systolic BP: -19.98 mmHg (90% CI, -30.52, -9.43), P < 0.002], [diastolic BP: -5.49 mmHg (90% CI, -11.38, 0.39), P = NS]. These BP changes were accompanied by a significant MSNA reduction [-4.28 bursts/min (90% CI, -8.62, 0.06), P < 0.07], and by a significant heart rate decrease [-3.65 beats/min (90% CI, -5.49, -1.81), P < 0.001]. No significant relationship was detected beween the MSNA, systolic and diastolic BP changes induced by the procedure, this being the case also for heart rate. Our data show that the acute BP lowering responses to carotid baroreflex stimulation, although associated with a significant MSNA reduction, are not quantitatively related to the sympathomoderating effects of the procedure. This may suggest that these BP effects depend only in part on central sympathoinhibition, at least in the acute phase following the intervention.

The left ventricle increases contractility in response to baroreceptor unloading, which is sympathetically mediated in the anesthetized rat.

Contemporary discussion of the baroreflex includes the efferent vascular-sympathetic and cardiovagal arms. Since sympathetic postganglionic neurons also innervate the left ventricle (LV), it is often assumed that the LV produces a sympathetically mediated increase in contractility during baroreceptor unloading, but this has not been characterized using a load-independent index of contractility. We aimed to determine 1) whether LV contractility increases in response to baroreceptor unloading and 2) whether such increases are mediated via the sympathetic or parasympathetic arm of the autonomic nervous system. Ten male Wistar rats were anesthetized (urethane) and instrumented with arterial and LV pressure-volume catheters to measure mean arterial pressure (MAP) and load-independent LV contractility [maximal rate of increase in pressure adjusted to end-diastolic volume (PAdP/dtmax)], respectively. Rats were placed in a servo-controlled lower-body negative pressure (LBNP) chamber to reduce MAP by 10% for 60 s to mechanically unload baroreceptors under control conditions. LBNP was repeated in each animal following infusions of cardiac autonomic blockers using esmolol (sympathetic), atropine (parasympathetic), and esmolol + atropine. Under control conditions, PAdP/dtmax increased during baroreceptor unloading (26 ± 6 vs. 31 ± 9 mmHg·s-1·µL-1, P = 0.031). During esmolol, there was no increase in LV contractility during baroreceptor unloading (11 ± 2 vs. 12 ± 2, P = 0.125); however, during atropine, there was an increase in LV contractility during baroreceptor unloading (26 ± 6 vs. 31 ± 9, P = 0.019). During combined esmolol and atropine, there was a small increase in contractility versus control (13 ± 3 vs. 15 ± 4, P = 0.046). Our results demonstrate that, in anesthetized rats, LV contractility increases in response to baroreceptor unloading, which is largely sympathetically mediated.NEW & NOTEWORTHY This study empirically demonstrates a sympathetically mediated increase in LV contractility in response to baroreceptor unloading using a load-independent index of cardiac contractility in the anesthetized rat.

Influence of sex on sympathetic vasomotor outflow responses to passive leg raising in young individuals.

The purpose of this study was to clarify sex differences in the inhibition of sympathetic vasomotor outflow which is caused by the loading of cardiopulmonary baroreceptors. Ten young males and ten age-matched females participated. The participants underwent a passive leg raising (PLR) test wherein they were positioned supine (baseline, 0º), and their lower limbs were lifted passively at 10º, 20º, 30º, and 40º. Each angle lasted for 3 min. Muscle sympathetic nerve activity (MSNA) was recorded via microneurography of the left radial nerve. Baseline MSNA was lower in females compared to males. MSNA burst frequency was decreased during the PLR in both males (- 6.2 ± 0.4 bursts/min at 40º) and females (- 6.5 ± 0.4 bursts/min at 40º), but no significant difference was detected between the two groups (P = 0.61). These results suggest that sex has minimal influence on the inhibition of sympathetic vasomotor outflow during the loading of cardiopulmonary baroreceptors in young individuals.

Arterial pulses link heart-brain oscillations.

A central baroreceptor monitors arterial pressure to modulate brain activity.

Blood pressure pulsations modulate central neuronal activity via mechanosensitive ion channels.

The transmission of the heartbeat through the cerebral vascular system causes intracranial pressure pulsations. We discovered that arterial pressure pulsations can directly modulate central neuronal activity. In a semi-intact rat brain preparation, vascular pressure pulsations elicited correlated local field oscillations in the olfactory bulb mitral cell layer. These oscillations did not require synaptic transmission but reflected baroreceptive transduction in mitral cells. This transduction was mediated by a fast excitatory mechanosensitive ion channel and modulated neuronal spiking activity. In awake animals, the heartbeat entrained the activity of a subset of olfactory bulb neurons within ~20 milliseconds. Thus, we propose that this fast, intrinsic interoceptive mechanism can modulate perception-for example, during arousal-within the olfactory bulb and possibly across various other brain areas.

Evaluating Total Atherosclerosis Burden of Baroreceptor-Resident Arteries after Ischemic Cerebrovascular Disease for Identifying Patients with Heavy Coronary Atherosclerosis Burden.

AIM: The carotid sinuses and aortic arch are baroreceptor-resident arteries (BRAs) and atherosclerosis-susceptible sites of brain-supplying arteries, which would impair baroreflex-mediated blood pressure (BP) regulation and prompt coronary atherosclerosis. We sought to determine the relationship between total atherosclerosis burden (TAB) of BRAs and coronary atherosclerosis burden (AB) in patients with ischemic cerebrovascular disease (ICVD) and explore the potential contribution of BP profiles to this relationship. METHODS: In this cross-sectional analysis of patients with ICVD who simultaneously undertook computed tomography angiography and 24-hour ambulatory BP monitoring, TAB of BRAs was scored based on the atherosclerotic vessel circumference ratio of the carotid sinuses and aortic arch, while the ABs of the intracranial, cervical, aortic, and coronary arteries were scored based on stenosis severity and plaque complexity as routine. RESULTS: Among the 230 patients analyzed, coronary AB was significantly correlated with TAB of BRAs, independently of, and more tightly than the ABs of the intracranial, cervical, and aortic arteries, and the stenosis- and complexity-based AB of BRA-located arteries (bilateral common and extracranial internal carotid arteries and aortic arch). Both coronary AB and TAB of BRAs were negatively associated with the night-to-day BP dipping ratios, which was quite different from the relationship between intracranial AB and 24-hour BP characteristics. These findings were also true for patients with ICVD without a history of coronary artery disease. CONCLUSION: Evaluating TAB of BRAs might provide a new link between atherosclerosis of brain- and heart-supplying arteries, connected partially by BP circadian rhythm. It might facilitate identifying patients with ICVD with heavy coronary AB and comprehensively managing vascular risk.

Key challenges in exploring the rat as a preclinical neurostimulation model for aortic baroreflex modulation in hypertension.

Electrode-based electrophysiological interfaces with peripheral nerves have come a long way since the 1960s, with several neurostimulation applications witnessing widespread clinical implementation since then. In resistant hypertension, previous clinical trials have shown that "carotid" baroreflex stimulation using device-based baroreflex activation therapy (BAT) can effectively lower blood pressure (BP). However, device-based "aortic" baroreflex stimulation remains untouched for clinical translation. The rat is a remarkable animal model that facilitates exploration of mechanisms pertaining to the baroreceptor reflex and preclinical development of novel therapeutic strategies for BP modulation and hypertension treatment. Specifically, the aortic depressor nerve (ADN) in rats carries a relatively pure population of barosensitive afferent neurons, which enable selective investigation of the aortic baroreflex function. In a rat model of essential hypertension, the spontaneously hypertensive rat (SHR), we have recently investigated the aortic baroreceptor afferents as an alternate target for BP modulation, and showed that "low intensity" stimulation is able to evoke clinically meaningful reductions in BP. Deriving high quality short-term and long-term data on aortic baroreflex modulation in rats is currently hampered by a number of unresolved experimental challenges, including anatomical variations across rats which complicates identification of the ADN, the use of unrefined neurostimulation tools or paradigms, and issues arising from anesthetized and conscious surgical preparations. With the goal of refining existing experimental protocols designed for preclinical investigation of the baroreflex, this review seeks to outline current challenges hindering further progress in aortic baroreflex modulation studies in rats and present some practical considerations and recently emerging ideas to overcome them. Aortic baroreflex modulation.

Input-size dependence of the baroreflex neural arc transfer characteristics during Gaussian white noise inputs.

Although Gaussian white noise (GWN) inputs offer a theoretical framework for identifying higher-order nonlinearity, an actual application to the data of the neural arc of the carotid sinus baroreflex did not succeed in fully predicting the well-known sigmoidal nonlinearity. In the present study, we assumed that the neural arc can be approximated by a cascade of a linear dynamic (LD) component and a nonlinear static (NS) component. We analyzed the data obtained using GWN inputs with a mean of 120 mmHg and standard deviations (SDs) of 10, 20, and 30 mmHg for 15 min each in anesthetized rats (n = 7). We first estimated the linear transfer function from carotid sinus pressure to sympathetic nerve activity (SNA) and then plotted the measured SNA against the linearly predicted SNA. The predicted and measured data pairs exhibited an inverse sigmoidal distribution when grouped into 10 bins based on the size of the linearly predicted SNA. The sigmoidal nonlinearity estimated via the LD-NS model showed a midpoint pressure (104.1 ± 4.4 mmHg for SD of 30 mmHg) lower than that estimated by a conventional stepwise input (135.8 ± 3.9 mmHg, P < 0.001). This suggests that the NS component is more likely to reflect the nonlinearity observed during pulsatile inputs that are physiological to baroreceptors. Furthermore, the LD-NS model yielded higher R2 values compared with the linear model and the previously suggested second-order Uryson model in the testing dataset.NEW & NOTEWORTHY We examined the input-size dependence of the baroreflex neural arc transfer characteristics during Gaussian white noise inputs. A linear dynamic-static nonlinear model yielded higher R2 values compared with a linear model and captured the well-known sigmoidal nonlinearity of the neural arc, indicating that the nonlinear dynamics contributed to determining sympathetic nerve activity. Ignoring such nonlinear dynamics might reduce our ability to explain underlying physiology and significantly limit the interpretation of experimental data.

Interaction of large artery stiffness and baroreceptor function explored through multiple measurement techniques - a pilot study.

Baroreceptors, sensors that play a role in controlling arterial blood pressure (BP), are mechanical stretch receptors located in the aortic arch and carotid sinuses. Factors affecting the degree of stretch in the vessel wall with BP, such as increased arterial stiffness, may compromise baroreceptor sensitivity (BRS) to BP changes. Yet, evidence of this is scattered, as both baroreceptor sensitivity (BRS) and arterial stiffness are calculated variables with multiple methodological approaches. This pilot study (n=10) investigates the correlation of arterial stiffness and BRS using multiple BRS calculation techniques (spectral and sequence methodologies at aortic and finger sites) and arterial stiffness measurement [carotid-femoral pulse wave velocity (cfPWV), carotid compliance and distensibility]. BRS was assessed under resting BP conditions and during BP altered by maneuvers (0.1 Hz controlled breathing and leg ischemia). Magnitude of arterial stiffness - BRS correlation was positive for carotid distensibility and compliance, and negative for cfPWV, supporting the theory. A sample size of 100 participants (not rounded - exact figure by power calculation) would be required to confirm or reject all permutations of correlation between BRS by multiple calculation methods and large artery stiffness by PWV and compliance/distensibility measures.

Rapid onset vasodilation during baroreceptor loading and unloading.

The purpose of these experiments was to determine if the increase in vascular conductance following a single muscle contraction (50% of maximal voluntary contraction) (6 male and 6 female subjects) was altered during baroceptor loading and unloading. Rapid onset vasodilation (ROV) was determined by measuring brachial artery blood flow (Doppler ultrasound) and blood pressure (Finapress monitor). Brachial artery vascular conductance was calculated by dividing blood flow by mean arterial pressure. ROV was described by the area under the Δvascular conductance (VC)-time curve during the 30 s following muscle contraction. ROV was determined using chamber pressures of +20, +10, 0, -10, -20, and -40 mmHg (lower body positive and negative pressure, LBPP, and LBNP). We tested the hypothesis that the impact of baroreceptor loading and unloading produces a proportion change in ROV. The level of ROV following each contraction was proportional to the peak force (r2 = 0.393, P = 0.0001). Peak force was therefore used as a covariate in further analysis. ROV during application of -40 mmHg LBNP (0.345 ± 0.229 mL·mmHg-1) was lower than that observed at Control (0.532 ± 0.284 mL·mmHg-1, P = 0.034) and +20 mmHg LBPP (0.658 ± 0.364 mL·mmHg-1, P = 0.0008). ROV was linearly related to chamber pressure from -40 to +20 mmHg chamber pressure (r2 = 0.512, P = 0.022, n = 69) and from -20 to +10 mmHg chamber pressure (r2= 0.973, P < 0.0425, n = 45), Overall, vasoconstrictor tone altered with physiologically relevant baroreceptor loading and unloading resulted in a proportion change in ROV.NEW & NOTEWORTHY Rapid onset vasodilation (ROV) was linearly related to the peak force of each single 1-s muscle contraction. In addition, ROV is reduced by baroreceptor unloading (LBNP: -10, -120, and -40 mmHg) and increased by baroreceptor loading (LBPP: +10 and +20 mmHg). Without accounting for peak force and the level of baroreceptor engagement makes comparison of ROV in subjects of differing muscle size or strength untenable.

Experimental carotid baroreceptor stimulation reduces blood flow velocities in the anterior and middle cerebral arteries of healthy individuals.

This study investigated effects of experimental baroreceptor stimulation on bilateral blood flow velocities in the anterior and middle cerebral arteries (ACA and MCA) using functional transcranial Doppler sonography. Carotid baroreceptors were stimulated by neck suction in 33 healthy participants. Therefore, negative pressure (- 50 mmHg) was applied; neck pressure (+ 10 mmHg) was used as a control condition. Heart rate (HR) and blood pressure (BP) were also continuously recorded. Neck suction led to reductions in bilateral ACA and MCA blood flow velocities, which accompanied the expected HR and BP decreases; HR and BP decreases correlated positively with the ACA flow velocity decline. The observations suggest reduction of blood flow in the perfusion territories of the ACA and MCA during baroreceptor stimulation. Baroreceptor-related HR and BP decreases may contribute to the cerebral blood flow decline. The findings underline the interaction between peripheral and cerebral hemodynamic regulation in autoregulatory control of cerebral perfusion.

Functional symmetry of the aortic baroreflex in female spontaneously hypertensive rats.

BACKGROUND: Altered baroreflex function is well documented in hypertension; however, the female sex remains far less studied compared with males. We have previously demonstrated a left-sided dominance in the expression of aortic baroreflex function in male spontaneously hypertensive rats (SHRs) and normotensive rats of either sex. If lateralization in aortic baroreflex function extends to hypertensive female rats remains undetermined. This study, therefore, assessed the contribution of left and right aortic baroreceptor afferents to baroreflex modulation in female SHRs. METHOD: Anesthetized female SHRs (total n  = 9) were prepared for left, right and bilateral aortic depressor nerve (ADN) stimulation (1-40 Hz, 0.2 ms, 0.4 mA for 20 s) and measurement of reflex mean arterial pressure (MAP), heart rate (HR), mesenteric vascular resistance (MVR) and femoral vascular resistance (FVR). All rats were also matched for the diestrus phase of the estrus cycle. RESULTS: Reflex (%) reductions in MAP, HR, MVR and FVR were comparable for both left-sided and right-sided stimulation. Bilateral stimulation evoked slightly larger ( P  = 0.03) reductions in MVR compared with right-sided stimulation; however, all other reflex hemodynamic measures were similar to both left-sided and right-sided stimulation. CONCLUSION: These data show that female SHRs, unlike male SHRs, express similar central integration of left versus right aortic baroreceptor afferent input and thus show no laterization in the aortic baroreflex during hypertension. Marginal increases in mesenteric vasodilation following bilateral activation of the aortic baroreceptor afferents drive no superior depressor responses beyond that of the unilateral stimulation. Clinically, unilateral targeting of the left or right aortic baroreceptor afferents may provide adequate reductions in blood pressure in female hypertensive patients.