Baroreceptor Activity Research Articles

P94 Hydrogen sulfide facilitates carotid sinus baroreceptor reflex and activity of renovascular hypertensive rats

To explore the role and possible mechanism of hydrogen sulfide (H 2 S) in modulating carotid sinus baroreceptor reflex and activity of renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by placing renal artery clip (two-kidney, one-clip; 2K1C).The functional curve of the carotid sinus baroreflex was measured by recording changes in arterial pressure with perfused carotid sinus. The functional curve of carotid baroreceptor (FCCB) was constructed by recording sinus nerve afferent discharge with perfused isolated carotid sinus. The expression of SUR2B and Kir6.1 of carotid sinus was examined. The systolic blood pressure (SBP) was significantly increased in the 2K1C group (172 ± 6.32 mmHg) comparing with the NaHS-treated group (134 ± 5.74 mmHg) ( P < 0.01). The plasma H 2 S concentration was decreased in the 2K1C group comparing with other groups. Perfusing the left carotid sinus with K-H solution and elevating the ISP from 0 to 250 mmHg. The reflexly decreased extent of blood pressure was obviously decreased in 2K1C group compared with other groups. The 2K1C group induced obvious changes in baroreflex parameters, marked decrease in RD and PS, and increased in TP, EP and SP, shifting the functional curve of the baroreflex to the right and upward. At the same time, the 2K1C group induced obvious changes in carotid sinus baroreceptor parameters, decreased PIV and PS, and increased TP and SP, shifting FCCB to the right and downward. All of these results were changed after the treatment of NaHS. SUR2B protein expression was higher in carotid sinus of the 2K1C + NaHS group than that of the 2K1C group. These data suggested that exogenous H 2 S exerted a facilitatory role on isolated baroreceptor reflex and activity in renovascular hypertensive rats through opening K ATP channels in vascular smooth muscle cells.

Carotid Baroreceptor Stimulation: A Promising Approach for the Management of Resistant Hypertension and Heart Failure

Many difficult-to-treat clinical entities in the cardiovascular field are characterized by pronounced sympathetic overactivity, including resistant hypertension and heart failure, underlining the need to explore therapeutic options beyond pharmacotherapy. Autonomic modulation via carotid baroreceptor activation has already been evaluated in clinical trials for resistant hypertension, and relevant outcomes with regard to safety and efficacy of the technique are critically presented. The pathophysiological background of heart failure renders carotid baroreceptor stimulation a potential treatment candidate for the disease. Available data from animal models with heart failure point towards significant cardioprotective benefits of this innovative technique. Accordingly, the effects of baroreceptor activation treatment (BAT) on cardiac parameters of hypertensive patients are well-promising, setting the basis for upcoming clinical trials with baroreflex activation on patients with heart failure. However, as the potential therapeutic of BAT unfolds and new perspectives are highlighted, several concerns are raised that should be meticulously addressed before the wide application of this invasive procedure is set in the limelight.

Functional neural-bone marrow pathways: implications in hypertension and cardiovascular disease.

Treatment-resistant hypertension (TRHT) is characterized by persistently high arterial blood pressure (BP), partly as a result of a dysfunctional autonomic nervous system (ANS), wherein sympathetic drive/norepinephrine spillover is increased and parasympathetic drive is decreased.1–3 The difficulty in treatment of TRHT arises precisely from this partly neurogenic component because the available drug therapies do not target the central nervous system (CNS) directly. Because of this and despite recent advances in techniques such as renal denervation and carotid baroreceptor activation,4,5 successful treatment and long-term control of TRHT remain challenging.6 In an attempt to develop more effective treatments, many groups are investigating specific causes of TRHT. A large body of experimental evidence implicates both genetic and environmental influences, such as salt sensitivity and elevated systemic renin–angiotensin system (RAS) activity7–14 in the pathophysiology of this disease. Furthermore, a majority of studies point to dysregulations in the activity within the cardiorespiratory brain regions as a reason for increased sympathetic and decreased parasympathetic drive to the peripheral organs,14–21 resulting in end-organ damage,21–25 vascular/endothelial dysfunction,26,27 and hormonal imbalance,28 which perpetuate the pathophysiology and complicate treatment strategies. Despite our increasing understanding of TRHT, the origins of this brain dysregulation remain largely unknown. Recently, the activity of the immune system29–31 and neuroimmune pathways in patients with hypertension and animal models of hypertension has been highlighted.32–36 Studies suggest that both the sympathetic and the parasympathetic arms of the ANS can exert their influence on the activity of the immune organs, tissues, and cells, and that it is the dysfunctional ANS-immune communication that may lead to hypertension and CVD.35–40 The aim of this review is to summarize the latest advances in this …

The Pathophysiological Basis of Carotid Baroreceptor Stimulation for the Treatment of Resistant Hypertension

The prevalence of resistant hypertension and existing limitations in antihypertensive drug therapy renders the interventional management of hypertension an attractive alternative. Carotid baroreceptors have been traditionally thought to be implicated only in short-term blood pressure regulation; however recent evidence suggests that the baroreceptors might play an important role even in the long-term blood pressure regulation. Electrical baroreflex stimulation appears safe and effective and might represent a useful adjunct to medical therapy in patients with resistant hypertension. This review endeavors to summarize the complex pathophysiology of blood pressure regulation, to describe the baroreflex circuit, its anatomy and physiology, to present previous data refuting a role for the baroreceptors in the long-term control of blood pressure and recent animal and human data suggesting an effective role of carotid baroreceptor activation in long-lasting blood pressure reduction. In this paper we attempt to critically evaluate existing information in this area and provide the scientific basis for carotid baroreceptor stimulation in the management of resistant hypertension.

Early Effects in Perivascular Nerves and Arterial Media Following Renal Artery Denervation

In the past years 2 different innovative methods of hypertension treatments were investigated. The first is the promising examination of the electrical activation of the carotid baroreceptors, which is now in the phase III studies,1,2 and second the usage of selective renal sympathetic denervation (RSD) as an alternative treatment in therapy-resistant hypertension. RSD is thought to be based on alteration of the sympathetic innervation of kidney and secondary effects on the renin–angiotensin–aldosterone system. The renal nerves are located in close vicinity to the renal artery wall. Their activation could be important for the progression of therapy-resistant hypertension. In this context, Krum et al3 showed the proof of principle of a percutaneous, catheter-based trail to destroy renal sympathetic nerves by the introduction of a RF catheter into the lumen of the main renal artery and its subsequent connection to a radiofrequency generator. Until recently, the renal denervation seemed to be a promising therapy option for antihypertensive treatment. However, the simplicity HTN-3 study as recently announced4 indicated a lack of effect of RSD. Nevertheless, at present, the underlying molecular mechanisms remain unclear during RSD. RF injury might damage the tissue by thermal coagulation but may also cause apoptosis as observed in colon cancer.5 Thus, we made up the hypothesis that RSD may induce apoptosis in the perivascular nerves. The initiation of apoptosis is still not entirely understood. One important pathway is the release of apoptosis-inducing factor (AIF) from the mitochondrial intermembrane space together with cytochrome c .6 Subsequently, AIF translocates to the nucleus and induces chromatin decondensation and DNA degradation, likely by endonucleases. Typically, when inducing apoptosis, AIF and caspases act together. However, AIF may induce cell death in a caspase-independent manner.7 The extrinsic pathway …

Chapter 1 - Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympathetic nervous system

Respiratory modulation seen in the sympathetic nerve activity (SNA) implies that the respiratory and sympathetic networks interact. During hypertension elicited by chronic intermittent hypoxia (CIH), the SNA displays an enhanced respiratory modulation reflecting strengthened interactions between the networks. In this chapter, we review a series of experimental and modeling studies that help elucidate possible mechanisms of sympatho-respiratory coupling. We conclude that this coupling significantly contributes to both the sympathetic baroreflex and the augmented sympathetic activity after exposure to CIH. This conclusion is based on the following findings. (1) Baroreceptor activation results in perturbation of the respiratory pattern via transient activation of postinspiratory neurons in the Bötzinger complex (BötC). The same BötC neurons are involved in the respiratory modulation of SNA, and hence provide an additional pathway for the sympathetic baroreflex. (2) Under hypercapnia, phasic activation of abdominal motor nerves (AbN) is accompanied by synchronous discharges in SNA due to the common source of this rhythmic activity in the retrotrapezoid nucleus (RTN). CIH conditioning increases the CO2 sensitivity of central chemoreceptors in the RTN which results in the emergence of AbN and SNA discharges under normocapnic conditions similar to those observed during hypercapnia in naïve animals. Thus, respiratory-sympathetic interactions play an important role in defining sympathetic output and significantly contribute to the sympathetic activity and hypertension under certain physiological or pathophysiological conditions, and the theoretical framework presented may be instrumental in understanding of malfunctioning control of sympathetic activity in a variety of disease states.

GABAergic Excitation of Vasopressin Neurons

Rationale: Increased arginine-vasopressin (AVP) secretion is a key physiological response to hyperosmotic stress and may be part of the mechanism by which high-salt diets induce or exacerbate hypertension. Objective: Using deoxycorticosterone acetate-salt hypertension model rats, we sought to test the hypothesis that changes in GABA A receptor–mediated inhibition in AVP-secreting magnocellular neurons contribute to the generation of Na + -dependent hypertension. Methods and Results: In vitro gramicidin-perforated recordings in the paraventricular and supraoptic nuclei revealed that the GABAergic inhibition in AVP-secreting neurons was converted into excitation in this model, because of the depolarization of GABA equilibrium potential. Meanwhile, in vivo extracellular recordings in the supraoptic nuclei showed that the GABAergic baroreflexive inhibition of magnocellular neurons was transformed to excitation, so that baroreceptor activation may increase AVP release. The depolarizing GABA equilibrium potential shift in AVP-secreting neurons occurred progressively over weeks of deoxycorticosterone acetate-salt treatment along with gradual increases in plasma AVP and blood pressure. Furthermore, the shift was associated with changes in chloride transporter expression and partially reversed by bumetanide (Na + -K + -2Cl – cotransporter inhibitor). Intracerebroventricular bumetanide administration during deoxycorticosterone acetate-salt treatment hindered the development of hypertension and rise in plasma AVP level. Muscimol (GABA A agonist) microinjection into the supraoptic nuclei in hypertensive rats increased blood pressure, which was prevented by previous intravenous V1a AVP antagonist injection. Conclusions: We conclude that the inhibitory-to-excitatory switch of GABA A receptor–mediated transmission in AVP neurons contributes to the generation of Na + -dependent hypertension by increasing AVP release. We speculate that normalizing the GABA equilibrium potential may have some utility in treating Na + -dependent hypertension.

Extracorporeal carbon dioxide removal: Effect of short time infusion of 3 different metabolic acids

Objectives: The measures of heart rate variability (HRV) can be classified into multiple domains of variability, depending on their theoretical background and method of computation; however, their physiological interpretation and degree of mutually independent information remain unknown, especially given that multiple measures of variability across domains are correlated with each other. The objective of this study was to investigate independence and ability to detect change of a set of measures of HRV in silico. Methods: To understand the physiological meaning of HRV, we used a physiologically based mathematical model from Kotani et al (2005). By altering its parameters, this model is able to produce R-R interval time series showing the scale-invariant properties of both healthy subjects and patients affected by heart diseases. We used Kotani's model to generate a set of R-R interval time series in the healthy case and in altered physiological conditions (ie, when the values of selected parameters of the model are modified) in order to investigate (1) the degree of independence of a set of measures of variability from multiple domains based on their mutual information and (2) their ability to sense changes in the physiological parameters of Kotani's model and to track them over time. Results: Our results show that, in the healthy cardiovascular system state of the model, the investigated HRV measures present low mutual information and, therefore, high degree of statistical independence. When the physiological conditions are altered by modifying the values of the parameters of Kotani's model, the measures follow those changes either increasing or decreasing their values. Each HRV measure resulted sensitive to multiple changes in the physiological conditions, in particular sympathetic and parasympathetic activity, baroreceptor activity, contractility of the heart, and respiration. Correlation analysis confirmed that the alteration of HRV measures due to changes in the physiological conditions leads to higher levels of correlation among the measures. Conclusions: The results suggest that each measure of HRV is a nonspecific sensor of the cardiovascular system. Because of the independence of HRV measures under baseline conditions as well as their partial correlation following physiological changes, the combination of multiple measures into composite indexes can enhance the “common” information related to physiological changes. This approach could be used to improve our understanding of cardiovascular physiology and translate the acquired knowledge into clinical applications.

Autocrine/paracrine modulation of baroreceptor activity after antidromic stimulation of aortic depressor nerve in vivo

Activation of the sensory nerve endings of non-myelinated C-fiber afferents evokes release of autocrine/paracrine factors that cause localized vasodilation, neurogenic inflammation, and modulation of sensory nerve activity. The aims of this study were to determine the effect of antidromic electrical stimulation on afferent baroreceptor activity in vivo, and investigate the role of endogenous prostanoids and hydrogen peroxide (H2O2) in mediating changes in nerve activity. Baroreceptor activity was recorded from the left aortic depressor nerve (ADN) in anesthetized rats before and after stimulating the ADN for brief (5–20 s) periods. The rostral end of the ADN was crushed or sectioned beforehand to prevent reflex changes in blood pressure. Antidromic stimulation of ADN using parameters that activate both myelinated A-fibers and non-myelinated C-fibers caused pronounced and long-lasting (> 1 min) inhibition of baroreceptor activity (n = 9, P < 0.05), with the magnitude and duration of inhibition dependent on the duration of the stimulation period (n = 5). Baroreceptor activity was only transiently inhibited after selective stimulation of A-fibers. The inhibition of activity after antidromic stimulation of A and C fibers was prolonged after administration of the cyclooxygenase inhibitor indomethacin (5 mg/kg, IV, n = 7) and abolished after administration of PEG-catalase (104 units/kg, IV, n = 7), an enzyme that catalyzes the decomposition of H2O2 to water and oxygen. The results demonstrate a long-lasting inhibition of baroreceptor activity after antidromic stimulation of ADN and suggest that endogenous prostanoids and H2O2 oppose and mediate the inhibition, respectively. These mechanisms may contribute to rapid baroreceptor resetting during acute hypertension and be engaged during chronic baroreceptor activation therapy in patients with hypertension.

The possibility of resistant hypertension during the treatment of hypertensive patients

Patients with poorly controlled hypertension despite taking at least three different kinds of anti-hypertensive drugs, including diuretics, are considered to have resistant hypertension (RH). The prevalence of RH was reported to be 13% in the Japanese J-HOME study. The incidences of RH in younger and older Japanese individuals should be prospectively investigated in the near future. RH is associated with poor outcomes and various cardiovascular events. In addition, it is frequently associated with older age, obesity, sleep apnea, long-term hypertension, diabetes, dyslipidemia, reduced renal function, microalbuminuria and left ventricular hypertrophy. Some cases of RH exhibit high levels of aldosterone and cortisol, suggesting that endocrine hypertension should be ruled out among RH patients. Carotid baroreceptor activation and renal sympathetic denervation have recently been developed as treatments for RH. In conclusion, we should consider the possibility of RH during the treatment of hypertensive patients who do not achieve appropriate blood pressure control, in order to avoid the early onset of fatal cardiovascular events and reduce medical costs.

Baroreflex-mediated cardiovascular responses to hyperbaric oxygen

The cardiovascular system responds to hyperbaric hyperoxia (HBO2) with vasoconstriction, hypertension, bradycardia, and reduced cardiac output (CO). We tested the hypothesis that these responses are linked by a common mechanism-activation of the arterial baroreflex. Baroreflex function in HBO2 was assessed in anesthetized and conscious rats after deafferentation of aortic or carotid baroreceptors or both. Cardiovascular and autonomic responses to HBO2 in these animals were compared with those in intact animals at 2.5 ATA for conscious rats and at 3 ATA for anesthetized rats. During O2 compression, hypertension was greater after aortic or carotid baroreceptor deafferentation and was significantly more severe if these procedures were combined. Similarly, the hyperoxic bradycardia observed in intact animals was diminished after aortic or carotid baroreceptor deafferentation and replaced by a slight tachycardia after complete baroreceptor deafferentation. We found that hypertension, bradycardia, and reduced CO--the initial cardiovascular responses to moderate levels of HBO2--are coordinated through a baroreflex-mediated mechanism initiated by HBO2-induced vasoconstriction. Furthermore, we have shown that baroreceptor activation in HBO2 inhibits sympathetic outflow and can partially reverse an O2-dependent increase in arterial pressure.

Plasma leptin inhibits the response of nucleus of the solitary tract neurons to aortic baroreceptor stimulation

Leptin receptors have been identified within the nucleus of the solitary tract (NTS) and leptin injections into the caudal NTS inhibit the baroreceptor reflex. However, whether plasma leptin alters the discharge of NTS neurons mediating aortic baroreceptor reflex activity is not known. A series of electrophysiological single unit recording experiments was done in the urethane-chloralose anesthetized, paralyzed and artificially ventilated Wistar and Zucker obese rat with either their neuroaxis intact or with mid-collicular transections. Single units in NTS antidromically activated by electrical stimulation of depressor sites in the caudal ventrolateral medulla (CVLM) were found to display a cardiac cycle-related rhythmicity. These units were tested for their responses to stimulation of the aortic depressor nerve (ADN) and intra-carotid injections of leptin (50-200ng/0.1ml). Of 63 single units tested in NTS, 33 were antidromically activated by stimulation of CVLM depressor sites and 18 of these single units responded with a decrease in discharge rate after intracarotid injections of leptin. Thirteen of these leptin responsive neurons (∼72%) were excited by ADN stimulation. Furthermore, the excitatory response of these single units to ADN stimulation was attenuated by about 50% after the intracarotid leptin injection. Intracarotid injections of leptin (200ng/0.1ml) in the Zucker obese rat did not alter the discharge rate of NTS-CVLM projecting neurons. These data suggest that leptin exerts a modulatory effect on brainstem neuronal circuits that control cardiovascular responses elicited during the reflex activation of arterial baroreceptors.

Arterial Baroreceptor Reflex Counteracts Long-Term Blood Pressure Increase in the Rat Model of Renovascular Hypertension

IntroductionThe present study tested the hypothesis that long-term effects of baroreceptor activation might contribute to the prevention of persistent arterial blood pressure (BP) increase in the rat model of renovascular hypertension (HTN).MethodsRepetitive arterial baroreflex (BR) testing was performed in normo- and hypertensive rats. The relationship between initial arterial BR sensitivity and severity of subsequently induced two-kidney one-clip (2K1C) renovascular HTN was studied in Wistar rats. Additionally, the time course of changes in systolic BP (SBP) and cardiac beat-to-beat (RR) interval was studied for 8 weeks after the induction of 2K1C renovascular HTN in the rats with and without sinoaortic denervation (SAD). In a separate experimental series, cervical sympathetic nerve activity (cSNA) was assessed in controls, 2K1C rats, WKY rats, and SHR.ResultsThe inverse correlation between arterial BR sensitivity and BP was observed in the hypertensive rats during repetitive arterial BR testing. The animals with greater initial arterial BR sensitivity developed lower BP values after renal artery clipping than those with lower initial arterial BR sensitivity. BP elevation during the first 8 weeks of renal artery clipping in 2K1C rats was associated with decreased sensitivity of arterial BR. Although SAD itself resulted only in greater BP variability but not in persistent BP rise, the subsequent renal artery clipping invariably resulted in the development of sustained HTN. The time to onset of HTN was found to be shorter in the rats with SAD than in those with intact baroreceptors. cSNA was significantly greater in the 2K1C rats than in controls.ConclusionsArterial BR appears to be an important mechanism of long-term regulation of BP, and is believed to be involved in the prevention of BP rise in the rat model of renovascular HTN.

FRI0449 Evaluationg the effect of valsalva maneuver on pain occurring during knee injection: A prospective, randomized study

BackgroundIntra-articular injection of steroid is a common treatment for osteoarthritis of the knee and injection is a simple and reliable method However many people refuse it because of fear of...

Cardiorespiratory coupling of sympathetic outflow in humans: a comparison of respiratory and cardiac modulation of sympathetic nerve activity to skin and muscle

What is the central question of this study?Muscle sympathetic nerve activity (MSNA) is well known to be modulated by the arterial baroreceptors and respiration, but what are the magnitudes of cardiac and respiratory modulation of skin sympathetic nerve activity (SSNA), which primarily subserves thermoregulation?What is the main finding and what is its importance?Using direct microelectrode recordings of MSNA and SSNA in awake humans, we show that the magnitude of respiratory modulation of SSNA is identical to that of MSNA, the primary difference between the two sources of sympathetic outflow being the greater cardiac modulation of MSNA. This emphasises the role of the baroreceptors in entraining sympathetic outflow to muscle. It is well known that microelectrode recordings of skin sympathetic nerve activity (SSNA) in awake human subjects reveal spontaneous bursts of activity with no overt modulation by changes in blood pressure or respiration, in contrast to the clear cardiac and respiratory modulation of muscle sympathetic nerve activity (MSNA). However, cross-correlation analysis has revealed that, like individual muscle vasoconstrictor neurones, the firing of individual cutaneous vasoconstrictor neurones is temporally coupled to both the cardiac and respiratory rhythms during cold-induced cutaneous vasoconstriction, and the same is true of single sudomotor neurones during heat-induced sweating. Here, we used cross-correlation analysis to determine whether SSNA exhibits cardiac and respiratory modulation in thermoneutral conditions and to compare respiratory and cardiac modulation of SSNA with that of MSNA. Oligounitary recordings of spontaneous SSNA (n = 20) and MSNA (n = 18) were obtained during quiet, unrestrained breathing. Respiration was recorded by a strain-gauge transducer around the chest and ECG recorded by surface electrodes. Respiratory and cardiac modulation of SSNA and MSNA were quantified by fitting polynomial equations to the cross-correlation histograms constructed between the sympathetic spikes and respiration or ECG. The amplitude of the respiratory modulation (52.5 ± 3.4%) of SSNA was not significantly different from the amplitude of the cardiac modulation (46.6 ± 3.2%). Both were comparable to the respiratory modulation of MSNA (47.7 ± 4.2%), while cardiac modulation of MSNA was significantly higher (89.8 ± 1.5%). We conclude that SSNA and MSNA share similar levels of respiratory modulation, the primary difference between the two sources of sympathetic outflow being the marked cardiac modulation of MSNA provided by the baroreceptors.

Electrocutaneous pain thresholds are higher during systole than diastole

Arterial baroreceptors may modulate pain. Evidence suggests the neurophysiological correlates of pain are dampened during systole, when baroreceptors are stimulated, compared to diastole, when stimulation is minimal. However, the influence of the cardiac cycle on perception of pain remains unclear. This study examined pain thresholds in 49 healthy adults at seven intervals after the R-wave of the electrocardiogram, using an interleaved up-down staircase procedure. Electrocutaneous stimuli were delivered to the hand and participants indicated the presence or absence of pain. Pain thresholds were higher mid-cycle, indicative of pain attenuation during systole compared to diastole. Moderation analyses revealed no relationship between the magnitude of cardiac cycle-related modulation and tonic blood pressure. These findings suggest fluctuations in arterial baroreceptor activity across the cardiac cycle may influence pain in normotensive individuals; however, tonic blood pressure may not affect the magnitude of this pain modulation.

Baroreceptor unloading converts depressor responses elicited from the hypothalamic arcuate nucleus to pressor responses

The type of response elicited from the hypothalamic arcuate nucleus (ARCN) depends on the level of baroreceptor activity. It was hypothesized that baroreceptor unloading may determine the type of response elicited from the ARCN. This hypothesis was tested in urethane‐anesthetized adult male Wistar rats. Bilateral barodenervation converted decreases in mean arterial pressure (MAP) and greater splanchnic nerve activity (GSNA) elicited by chemical stimulation of the ARCN to increases in MAP and GSNA and exaggerated tachycardia. Microinjections of ionotropic glutamate receptor antagonists into the paraventricular nucleus (PVN) in barodenervated rats converted increases in MAP and GSNA elicited by the ARCN stimulation to decreases in MAP and GSNA and attenuated tachycardia. Microinjections of a melanocortin 3/4 receptor antagonist into the PVN in barodenervated rats attenuated increases in MAP, GSNA and heart rate elicited by the ARCN stimulation. ARCN neurons projecting to the PVN were immunoreactive for proopiomelanocortin, alphamelanocyte stimulating hormone (alpha‐MSH) and adrenocorticotropic hormone (ACTH).Conclusionincreases in MAP and GSNA and exaggeration of tachycardia elicited by the ARCN stimulation in barodenervated rats may be mediated via release of alpha‐MSH and/or ACTH and glutamate from the ARCN neurons projecting to the PVN. Support: NIH grants HL024347 and HL076248(HNS).

Leptin in nucleus of the solitary tract alters the cardiovascular responses to aortic baroreceptor activation

Recent data suggests that neurons expressing the long form of the leptin receptor form at least two distinct groups within the caudal nucleus of the solitary tract (NTS): a group within the lateral NTS (Slt) and one within the medial (Sm) and gelantinosa (Sg) NTS. Discrete injections of leptin into Sm and Sg, a region that receives chemoreceptor input, elicit increases in arterial pressure (AP) and renal sympathetic nerve activity (RSNA). However, the effect of microinjections of leptin into Slt, a region that receives baroreceptor input is unknown. Experiments were done in the urethane-chloralose anesthetized, paralyzed and artificially ventilated Wistar or Zucker obese rat to determine leptin's effect in Slt on heart rate (HR), AP and RSNA during electrical stimulation of the aortic depressor nerve (ADN). Depressor sites within Slt were first identified by the microinjection of l-glutamate (Glu; 0.25M; 10nl) followed by leptin microinjections. In the Wistar rat leptin microinjection (50ng; 20nl) into depressor sites within the lateral Slt elicited increases in HR and RSNA, but no changes in AP. Additionally, leptin injections into Slt prior to Glu injections at the same site or to stimulation of the ADN were found to attenuate the decreases in HR, AP and RSNA to both the Glu injection and ADN stimulation. In Zucker obese rats, leptin injections into NTS depressor sites did not elicit cardiovascular responses, nor altered the cardiovascular responses elicited by stimulation of ADN. Those data suggest that leptin acts at the level of NTS to alter the activity of neurons that mediate the cardiovascular responses to activation of the aortic baroreceptor reflex.

Proposal of a new strategy for ambulatory blood pressure profile-based management of resistant hypertension in the era of renal denervation

In Asian populations, a high prevalence of stroke, high salt intake and high salt sensitivity, the effects of which are partly augmented by epidemic obesity, are associated with hypertension. These factors are closely associated with resistant hypertension, especially with the disrupted circadian rhythm of blood pressure (BP), that is, non-dipper and riser patterns. An ambulatory BP profile-based strategy combined with medication and devices (renal denervation and baroreceptor activation therapy) would help to achieve 'perfect 24-h BP control', consisting of strict reduction of the 24-h BP level, restoring disrupted circadian BP rhythms and reducing excess BP variability. Such BP control would protect high-risk patients with resistant hypertension against systemic hemodynamic atherothrombotic syndrome (which involves systemic atherothrombotic vascular diseases and target-organ damage, advanced by the composite risks of pulsatile hemodynamic stress from central pressure and blood flow and by thrombometabolic risk factors). Information technology-based home sleep BP pressure monitoring may be useful for assessing the risk during sleep in high-risk patients with resistant hypertension and sleep apnea syndrome.

Low-frequency and very low-intensity ultrasound decreases blood pressure in subjects with hypertension

Despite lifestyle interventions and various types of anti-hypertension agents, high blood pressure remains difficult to control in some patients [1]. Device-based treatment approaches for resistant hypertension, such as catheter-based renal sympathetic denervation by radiofrequency ablation and baroreceptor activation therapy, have shown promising results in clinical trials [1–5]. These device-based approaches, however, are invasive and thus their therapeutic applications are limited in primary care.