ASIC2 Synergizes with TRPV1 in the Mechano-Electrical Transduction of Arterial Baroreceptors / 神经科学通报·英文版

Mechanosensitive ion channels (MSCs) are key molecules in the mechano-electrical transduction of arterial baroreceptors. Among them, acid-sensing ion channel 2 (ASIC2) and transient receptor potential vanilloid subfamily member 1 (TRPV1) have been studied extensively and documented to play important roles. In this study, experiments using aortic arch-aortic nerve preparations isolated from rats revealed that both ASIC2 and TRPV1 are functionally necessary, as blocking either abrogated nearly all pressure-dependent neural discharge. However, whether ASIC2 and TRPV1 work in coordination remained unclear. So we carried out cell-attached patch-clamp recordings in HEK293T cells co-expressing ASIC2 and TRPV1 and found that inhibition of ASIC2 completely blocked stretch-activated currents while inhibition of TRPV1 only partially blocked these currents. Immunofluorescence staining of aortic arch-aortic adventitia from rats showed that ASIC2 and TRPV1 are co-localized in the aortic nerve endings, and co-immunoprecipitation assays confirmed that the two proteins form a compact complex in HEK293T cells and in baroreceptors. Moreover, protein modeling analysis, exogenous co-immunoprecipitation assays, and biotin pull-down assays indicated that ASIC2 and TRPV1 interact directly. In summary, our research suggests that ASIC2 and TRPV1 form a compact complex and function synergistically in the mechano-electrical transduction of arterial baroreceptors. The model of synergism between MSCs may have important biological significance beyond ASIC2 and TRPV1.

Reflexo dos barorreceptores e homeostase da pressão arterial / Baroreflexes and blood pressure homeostasis

A hipertensão arterial é considerada um dos principais fatores de risco para a morbidade e mortalidade cardiovascular. Os reflexos originados nos barorreceptores arteriais e nos receptores de estiramento da região cardiopulmonar são os principais mecanismos de controle efetivo da pressão arterial a curto prazo. O reflexo dos barorreceptores é considerado um sistema de controle de alto ganho, que mantém a pressão arterial dentro de limites normais em períodos de segundos a minutos. Dessa forma, esta revisão busca abordar os mecanismos desenvolvidos pelos barorreceptores na homeostase da pressão arterial. No presente artigo foram relatadas as alterações dos reflexos cardiovasculares na hipertensão arterial, focando a distribuição dos barorreceptores e seu funcionamento no restabelecimento da pressão arterial. Para realização desta pesquisa foi realizada uma revisão de artigos científicos utilizando as bases de dados Medline, Scielo e Lilacs. Adicionalmente foram consultados livros de fisiologia humana para complementação das informações sobre a fisiologia do barorreflexo na homeostase da pressão arterial. Estudos clínicos têm mostrado que uma reduzida sensibilidade do barorreflexo está associada com a morte súbita que se segue ao infarto agudo do miocárdio. O entendimento dos reflexos dos barorreceptores e a manutenção da hipertensão arterial em curto prazo são de grande importância para o entendimento da fisiopatogenia envolvidas no desenvolvimento e/ou evolução de determinadas alterações patológicas (AU)

Hypertension is considered one of the main risk factors for cardiovascular morbidity and mortality. The reflexes of arterial baroreceptors and stretch receptors in the cardiopulmonary region are the primary mechanisms for effectively controlling arterial blood pressure in the short term. Baroreflexes are a relatively high gain control system that regulates blood pressure during short time periods such as seconds or minutes. This literature review aims to discuss the mechanisms developed by baroreceptors in blood pressure homeostasis. We describe the effects of cardiovascular reflexes on blood pressure, with focus on the distribution of baroreceptors and on its role in controlling blood pressure. Our research was based on scientific articles from the Medline, Scielo, and Lilacs databases. We also researched books on human physiology in order to describe the physiology of baroreflexes in blood pressure homeostasis. Clinical studies have shown that decreased baroreflex sensitivity is associated with sudden death following myocardial infarction. Understanding baroreflexes and short-term blood pressure regulation is essential for understanding the physiopathogenesis involved in the development of certain pathological changes (AU)

Effect of carotid and aortic baroreceptors on cardiopulmonary reflex: the role of autonomic function

We determined the sympathetic and parasympathetic control of heart rate (HR) and the sensitivity of the cardiopulmonary receptors after selective carotid and aortic denervation. We also investigated the participation of the autonomic nervous system in the Bezold-Jarish reflex after selective removal of aortic and carotid baroreceptors. Male Wistar rats (220-270 g) were divided into three groups: control (CG, N = 8), aortic denervation (AG, N = 5) and carotid denervation (CAG, N = 9). AG animals presented increased arterial pressure (12 percent) and HR (11 percent) compared with CG, while CAG animals presented a reduction in arterial pressure (16 percent) and unchanged HR compared with CG. The sequential blockade of autonomic effects by atropine and propranolol indicated a reduction in vagal function in CAG (a 50 and 62 percent reduction in vagal effect and tonus, respectively) while AG showed an increase of more than 100 percent in sympathetic control of HR. The Bezold-Jarish reflex was evaluated using serotonin, which induced increased bradycardia and hypotension in AG and CAG, suggesting that the sensitivity of the cardiopulmonary reflex is augmented after selective denervation. Atropine administration abolished the bradycardic responses induced by serotonin in all groups; however, the hypotensive response was still increased in AG. Although the responses after atropine were lower than the responses before the drug, indicating a reduction in vagal outflow after selective denervation, our data suggest that both denervation procedures are associated with an increase in sympathetic modulation of the vessels, indicating that the sensitivity of the cardiopulmonary receptors was modulated by baroreceptor fibers.

Control neural de la circulación periférica y de la presión arterial / Neural control of the peripheral circulation and blood pressure

In the XIX century Claude Bernard discovered the action of the nervous system on the peripheral circulation. In the first half of the XX century Ewald Hering discovered the baro-receptor and the reflex control of the heart rate and blood pressure. Cowley and Guyton demonstrated that sino-aortic denervation induces persistent changes in the blood pressure in the dog. The autonomic nervous system is mainly responsible for the regulation of the circulation and blood pressure in the short term on a beat to beat basis. It controls the vasomotor tone, the heart rate and the cardiac output. With the advent of non invasive methods that measure the blood pressure on a beat to beat basis (Finapres) and with the methods of measurement of the variability of the blood pressure in the frequency domain (spectral analysis) we can currently measure many variables including heart rate, blood pressure, stroke volume, peripheral resistances and the baroreceptor sensitivity and make some inferences about their control mechanisms. These variables can be measured at rest in the supine position, standing up, during rhythmic breathing and during the Valsalva maneuver. In this article we present a review of the neural control of the blood pressure and heart rate.

Evidence that blood pressure remains under the control of arterial baroreceptors in renal hypertensive rats

The purpose of the present study was to determine the range of the influence of the baroreflex on blood pressure in chronic renal hypertensive rats. Supramaximal electrical stimulation of the aortic depressor nerve and section of the baroreceptor nerves (sinoaortic denervation) were used to obtain a global analysis of the baroreceptor-sympathetic reflex in normotensive control and in chronic (2 months) 1-kidney, 1-clip hypertensive rats. The fall in blood pressure produced by electrical baroreceptor stimulation was greater in renal hypertensive rats than in normotensive controls (right nerve: -47 ± 8 vs -23 ± 4 mmHg; left nerve: -51 ± 7 vs -30 ± 4 mmHg; and both right and left nerves: -50 ± 8 vs -30 ± 4 mmHg; P < 0.05). Furthermore, the increase in blood pressure level produced by baroreceptor denervation in chronic renal hypertensive rats was similar to that observed in control animals 2-5 h (control: 163 ± 5 vs 121 ± 1 mmHg; 1K-1C: 203 ± 7 vs 170 ± 5 mmHg; P < 0.05) and 24 h (control: 149 ± 3 vs 121 ± 1 mmHg; 1K-1C: 198 ± 8 vs 170 ± 5 mmHg; P < 0.05) after sinoaortic denervation. Taken together, these data indicate that the central and peripheral components of the baroreflex are acting efficiently at higher arterial pressure in renal hypertensive rats when the aortic nerve is maximally stimulated or the activity is abolished.

Acute and chronic electrical activation of baroreceptor afferents in awake and anesthetized subjects

Electrical stimulation of baroreceptor afferents was used in the 1960's in several species, including human beings, for the treatment of refractory hypertension. This approach bypasses the site of baroreceptor mechanosensory transduction. Chronic electrical stimulation of arterial baroreceptors, particularly of the carotid sinus nerve (Hering's nerve), was proposed as an ultimate effort to treat refractory hypertension and angina pectoris due to the limited nature of pharmacological therapy available at that time. Nevertheless, this approach was abandoned in the early 1970's due to technical limitations of implantable devices and to the development of better-tolerated antihypertensive medications. More recently, our laboratory developed the technique of electrical stimulation of the aortic depressor nerve in conscious rats, enabling access to hemodynamic responses without the undesirable effect of anesthesia. In addition, electrical stimulation of the aortic depressor nerve allows assessment of the hemodynamic responses and the sympathovagal balance of the heart in hypertensive rats, which exhibit a well-known decrease in baroreflex sensitivity, usually attributed to baroreceptor ending dysfunction. Recently, there has been renewed interest in using electrical stimulation of the carotid sinus, but not the carotid sinus nerve, to lower blood pressure in conscious hypertensive dogs as well as in hypertensive patients. Notably, previous undesirable technical outcomes associated with electrical stimulation of the carotid sinus nerve observed in the 1960's and 1970's have been overcome. Furthermore, promising data have been recently reported from clinical trials that evaluated the efficacy of carotid sinus stimulation in hypertensive patients with drug resistant hypertension.

Baroreceptor mediated blood pressure regulation is not affected during dose dependent inhibition of prostatic contractions by terazosin.

Benign prostatic hyperplasia (BPH), common in aging males is often treated with alpha1-adrenoceptor (AR) antagonists. In view of known hypotensive effect of most of the alpha1-AR antagonists, this work examined the effect of a selected alpha1-AR antagonist, terazosin on the baroreceptor mediated regulation of blood pressure. The three doses of terazosin (10, 100, 300 microg/kg body weight) used in anesthetized dogs inhibited in a dose-dependent manner the prostatic contractions and rise in blood pressure induced by phenylphrine. Impairment of arterial baroreflex, an important neural regulatory mechanism for the maintenance of normal arterial pressure, by alpha1-AR antagonist (prazosin) has been suggested in an earlier study. Hence, the effects of terazosin in doses 10, 100 and 300 microg/kg on baroreflex sensitivity (calculated as the ratio of heart rate change to acute increase in blood pressure by phenylephrine) were investigated. Terazocin did not produce any change in the baroreflex sensitivity. Therefore, in the absence of any adverse effect on the baroreceptor mediated regulation of the blood pressure, terazosin can be treated as a safer drug for the symptomatic treatment of BPH.

Comparison of three methods for the determination of baroreflex sensitivity in conscious rats

Baroreflex sensitivity was studied in the same group of conscious rats using vasoactive drugs (phenylephrine and sodium nitroprusside) administered by three different approaches: 1) bolus injection, 2) steady-state (blood pressure (BP) changes produced in steps), 3) ramp infusion (30 s, brief infusion). The heart rate (HR) responses were evaluated by the mean index (mean ratio of all HR changes and mean arterial pressure (MAP) changes), by linear regression and by the logistic method (maximum gain of the sigmoid curve by a logistic function). The experiments were performed on three consecutive days. Basal MAP and resting HR were similar on all days of the study. Bradycardic responses evaluated by the mean index (-1.5 ñ 0.2, -2.1 ñ 0.2 and -1.6 ñ 0.2 bpm/mmHg) and linear regression (-1.8 ñ 0.3, -1.4 ñ 0.3 and -1.7 ñ 0.2 bpm/mmHg) were similar for all three approaches used to change blood pressure. The tachycardic responses to decreases of MAP were similar when evaluated by linear regression (-3.9 ñ 0.8, -2.1 ñ 0.7 and -3.8 ñ 0.4 bpm/mmHg). However, the tachycardic mean index (-3.1 ñ 0.4, -6.6 ñ 1 and -3.6 5 0.5 bpm/mmHg) was higher when assessed by the steady-state method. The average gain evaluated by logistic function (-3.5 ñ 0.6, -7.6 ñ 1.3 and -3.8 ñ 0.4 bpm/mmHg) was similar to the reflex tachycardic values, but different from the bradycardic values. Since different ways to change BP may alter the afferent baroreceptor function, the MAP changes obtained during short periods of time (up to 30 s: bolus and ramp infusion) are more appropriate to prevent the acute resetting. Assessment of the baroreflex sensitivity by mean index and linear regression permits a separate analysis of gain for reflex bradycardia and reflex tachycardia. Although two values of baroreflex sensitivity cannot be evaluated by a single symmetric logistic function, this method has the advantage of better comparing the baroreflex sensitivity of animals with different basal blood pressures

Baroreflex control of sympathetic activity in experimental hypertension

The arterial baroreceptor reflex system is one of the most powerful and rapidly acting mechanisms for controlling arterial pressure. The purpose of the present review is to discuss data relating sympathetic activity to the baroreflex control of arterial pressure in two different experimental models: neurogenic hypertension by sinoaortic denervation (SAD) and high-renin hypertension by total aortic ligation between the renal arteries in the rat. SAD depresses baroreflex regulation of renal sympathetic activity in both the acute and chronic phases. However, increased sympathetic activity (100 percent) was found only in the acute phase of sinoaortic denervation. In the chronic phase of SAD average discharge normalized but the pattern of discharges was different from that found in controls. High-renin hypertensive rats showed overactivity of the renin angiotensin system and a great depression of the baroreflexes, comparable to the depression observed in chronic sinoaortic denervated rats. However, there were no differences in the average tonic sympathetic activity or changes in the pattern of discharges in high-renin rats. We suggest that the difference in the pattern of discharges may contribute to the increase in arterial pressure lability observed in chronic sinoaortic denervated rats.

Influence of arterial baroreceptors as heart rate variability

Fluctuations in heart rate, blood pressure and other circulatory parameters have been described since the last century, but only recently the observation that changes in these fluctuations are associated with changes in the sympathovagal balance and with the activity of the arterial baroreflexes has led to the practical use of analysis of cardiovascular variability as a marker of autonomic function. The present review reports the various hypotheses on the origin of fluctuations in cardiovascular variability and the possibility to apply these observations to the clinical field. Method: Two main oscillatory components have been described in the cardiovascular system: one is related to the respiratory activity; a second component whose period is 10 s is independent of respiration. These can be accurately quantified by computerized methods based on spectral analysis. These fluctuations might not only be used as a marker of vagal and sympathetic activity, but also provide information on the activity of the arterial baroreflex. A practical approach to obtain this data is discussed. Practical implications of this methodology involve the non-invasive assessment of baroreflex activity and sympathovagal balance under a large number of physiologic and pathologic conditions. In this article the application to the autonomic assessment during physical exercise and after cardiac transplantation is reviewed in depth. Conclusions: The arterial baroreceptors exert a strong, though not exclusive influence on the cardiovascular fluctuations, through both sympathetic and vagal activity. These might be conveniently evaluated by non-invasive techniques involving spectral analysis of cardiovascular variability

Autonomic processing of the cardiovascular reflexes in the nucleus tractus solitarii

The nucleus tractus solitarii (NTS) receives afferent projections from the arterial baroreceptors, carotid chemoreceptors and cardiopulmonary receptors and as a function of this information produces autonomic adjustments in order to maintain arterial blood pressure within a narrow range of variation.The activation of each of these cardiovascular afferents produces a specific autonomic response by the excitation of neuronal projections from the NTS to the ventrolateral areas of the medulla (nucleus ambiguus, caudal and rostral ventrolateral medulla). The neurotransmitters at the NTS level as well as the excitatory amino acid (EAA) receptors involved in the processing of the autonomic responses in the NTS, although extensively studied, remain to be completely elucidated. In the present review we discuss the role of the EAA L-glutamate and its different receptor subtypes in the processing of the cardiovascular reflexes in the NTS. The data presented in this review related to the neurotransmission in the NTS are based on experimental evidence obtained in our laboratory in unanesthetized rats. The two major conclusions of the present review are that a) the excitation of the cardiovagal component by cardiovascular relfex activation (chemo- and Bezold-Jarisch reflexes) or by L-glutamatae microinjection into the NTS is mediated by N-methyl-D-aspartate (NMDA) receptors, and b) the sympatho-excitatory componente of the chemoreflex and the pressor response to L-glutamate microinjected into the NTS are not affected by an NMDA receptor antagonist, suggesting that the sympatho-excitatory component of these responses is mediated by non-NMDA receptors.

Effect of nifedipine on arterial pressure lability of sino-aortic deafferentated rats

Sino-aortic deafferentation (SAD) in rats produces arterial pressure lability (APL) whose mechanisms are not completely understood. In the present study we infused nifedipine (500 micro g kg(-1) min(-1)) for 30 min into sham-operated and acute SAD rats (24 h) and the changes in mean arterial pressure (MAP) and APL were measured during this period by a computerized technique. APL was reported as the standard deviation of the mean of all MAP sampling points. In SAD rats with high basal APL levels (SAD high APL, N = 8) nifedipine produced a significant reduction in MAP (from 116 +/- 5 to 88 +/- 3 mmHg) and APL (from 19.62 +/- 1.46 to 9.51 +/- 0.88 mmHg). while in SAD rats with low basal APL levels (SAD low APL, N = 8) it significantly reduced MAP (from 120 +/- 7 to 95 +/- 6 mmHg) and did not change APL (9.46 +/- 0.69 to 10.93 +/- 1.62). Nifedipine infusion into sham-operated rats (N = 8) produced no significant changes in MAP (105 +/- 3 vs 104 +/- 2 mmHg) or APL (4.17 +/- 0.53 vs 3.99 +/- 0.67 mmHg). Since nifedipine infusion reduced APL only in SAD high APL rats but reduced the MAP in both groups of SAD rats. we conclude that its effect on APL is not related to decreases in MAP. These data suggest that extracellular calcium influx through calcium channels plays an important role in the generation of APL, especially in SAD rats with high APL levels.

Relaçäo temporal entre atividade neurogênica dos pressoreceptores e atividade simpática periférica e labilidade da pressäo arterial / Temporal relation between neurogenic activity of pressoreceptors and peripheral sympathetic activity and arterial pressure lability

O objetivo desse estudo foi avaliar a atividade neurogênica dos pressoreceptores (APR, registrada no nervo aórtico) e a atividade simpática periférica (ASR, registrada no nervo simpático renal), considerando-se a ocorrência e distribuição nos ciclos cardíacos e nas fases sistólica e diastólica. Foram estudados ratos normais anestesiados e ratos acordados submetidos à desnervação sino-aórtica (DSA) nas fases aguda e crônica após a desnervação. Os resultados obtidos sugerem que a falta de sincronismo entre a atividade simpática e os ciclos da pressão arterial contribuem para as alterações encontradas na pressão sanguínea na ausência dos pressoreceptores

Abstract - The aim of this study was to analyze the neurogenic activity of baroreceptors (recorded on the aortic nerve, APR) and peripheral sympathetic activity (recorded on the renal nerve. AsR ) with regard to its occurence and distribution in relation to the cardiac cycle and the systolic and diastolic phases of it. Normal anesthetized rats and awaken sino aortic denervated (SAD) rats were studied. The analysis showed that the existing synchronism between sympathetic activity and arterial pressure pulses found in normal rats was absent in SAD rats. These results suggest that the Jack of synchronism between sympathetic activity and cardiac cycles may contribute to the alterations in blood pressure observed in the absence of baroreceptors

Effect of acute haemodilution on right atrial type-B receptor activity in anaesthetized cats.

In order to investigate whether the sensitivity of atrial type-B receptors to its natural stimulus is altered during acute haemodilution, experiments were conducted in nine anaesthetized, artificially ventilated and thoracotomized cats. Haemodilution was achieved by replacement of blood by the same volume of dextran (MW 150000). Atrial receptor activity, arterial blood pressure, right atrial pressure and ECG were recorded. Heart rate was calculated from ECG records. Arterial blood hematocrit was measured. Mean arterial blood pressure and heart rate were not altered by haemodilution even at a hematocrit level of 12.17 +/- 0.93 percent. Average activity of type-B atrial receptors, mean right atrial pressure, right atrial peak 'v' pressure, right atrial initial 'v' pressure and right atrial 'v' wave amplitude were changed significantly (r < 0.05) during acute haemodilution when the hematocrit was 12.17 +/- 0.93 percent but the atrial type-B receptor activity per cycle did not show any significant change. Average activity of type-B receptors increased from 8.56 +/- 1.02 spikes/sec to 9.56 +/- 1.11 spikes/sec. Mean right atrial pressure, right atrial 'v' wave amplitude, right atrial peak 'v' pressure increased significantly (P < 0.05) from respective control values. Right atrial initial 'v' wave pressure decreased significantly. Heart rate changed from 168.11 +/- 5.42 beats/min to 170.89 +/- 5.65 beats/min. Mean arterial pressure changed from 134.33 +/- 0.89 mmHg to 135.67 +/- 1.46 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Neural and humoral mechanisms involved in the generation of arterial pressure lability in rats

1. The role of the renin-angiotensin system (RAS) and sympathetic nervous system (SNS) in the generation of the arterial pressure lability (APL) observed after sino-aortic deafferentation (SAD) in rats was evaluated. 2. SAD was performed in normotensive (N = 8), renal hypertensive (2K-1C, N = 8) and spontaneously hypertensive rats (SHR, N = 8) and mean arterial pressure (MAP) recordings were performed 24 h after SAD. 3. MAP was recorded by a computerized technique using a sampling frequency of 30 Hz for 30 min and the data obtained were used to calculate APL. After MAP measurements the activity of the RAS and SNS was pharmacologically evaluated in all groups by the changes in MAP in response to iv injection of captopril and hexamethonium chloride, respectively. 4. SAD produced an increase in MAP (118 +/- 4 vs 99 +/- 2 mmHg) and a large increase in APL (13.4 +/- 1.3 vs 3.8 +/- 0.3 mmHg) in normotensive rats. SAD produced no changes in MAP (161 +/- 7 vs 167 +/- 7 mmHg) in 2K-1C hypertensive rats but induced a large increase in APL (6.7 +/- 0.5 vs 12 +/- 1 mmHg). SAD also produced no changes in MAP (152 +/- 3 vs 152 +/- 4 mmHg) in SHR but induced a marked increase in APL (6.7 +/- 0.3 vs 21 +/- 2.3 mmHg). 5. All SAD rats presented a larger fall in MAP in response to captopril and hexamethonium than the respective control group with intact baroreceptors suggesting an overactivity of both systems after SAD in normotensive, renal hypertensive and spontaneously hypertensive rats. 6. The data also show that SAD produced no additional increase in MAP but promoted a significant increase in APL in renal and spontaneously hypertensive rats. 7. We suggest that APL observed after SAD in different experimental models is dependent on an interaction of RAS and SNS, both of which seem to be overactive after removal of arterial baroreceptors

Effect of acute haemodilution on right atrial type-A receptor activity and right atrial pressure in anaesthetized cats.

To determine the effects of acute haemodilution on right atrial pressure and right atrial type-A receptor activity, experiments were conducted in nine anaesthetized cats. Haemodilution was induced by replacement of blood by same volume of dextran (molecular weight-150000). Arterial blood pressure, right atrial pressure and right atrial type-A receptor activity were recorded. Hematocrit, arterial blood pO2, pCO2, and pH were measured. Mean arterial blood pressure, pO2, pCO2, and pH were not altered by haemodilution which extended to a hematocrit level of about 13%. Mean right atrial pressure, 'a' wave pressure showed significant changes after 2nd and 3rd exchange. Heart rate and 'a' wave amplitude changed significantly (P < 0.05) after 3rd exchange. The amplitude of the 'a' wave was increased from 3.57 +/- 0.93 to 5.79 +/- 1.46 cm H2O, heart rate was increased from 163.89 +/- 5.36 to 169.22 +/- 4.84 beats/min, mean right atrial pressure was increased from 2.85 +/- 0.31 to 4.61 +/- 0.27 cm H2O, initial 'a' wave pressure was increased from 1.78 +/- 0.09 to 5.06 +/- 0.44 cm H2O. The data indicate that under present experimental conditions, the activity of the type-A receptor did not show any significant change (P > 0.05) on acute haemodilution. Significant increase (P < 0.05) in the amplitude of 'a' wave, mean right atrial pressure and initial 'a' wave pressure could be attributed to increased myocardial contractility.

Role of vagal and sinoaortic baroreflexes in circulatory adjustments to passive head up tilt.

To evaluate the contribution of vagal and sinoaortic baroreflexes in circulatory adjustments anaesthetized rabbits were subjected to 70 degree head up tilt with (i) both reflexes intact; (ii) after elimination of sinoaortic reflexes; (iii) after elimination of vagal reflexes; and (iv) after elimination of both categories of reflexes. The results suggest that vagal mediated baroreflexes from cardiopulmonary baroreceptors contribute significantly in circulatory adjustments to passive head up tilt while sinoaortic baroreflexes play the major role.