Carotid Sinus Baroreceptors Research Articles

Long-term effect of carotid endarterectomy on carotid sinus baroreceptor function and blood pressure control.

In order to assess whether carotid endarterectomy had any long-term hypotensive effect, by altering the function of the carotid sinus baroreceptors, blood pressure and carotid sinus baroreceptor function were recorded in 25 patients undergoing carotid endarterectomy. No overall change in blood pressure was recorded 6 months after surgery. Sinus function was shown to decrease in 2 (8 per cent), to remain unchanged in 15 (60 per cent) and to increase in 8 (32 per cent) patients 6 months postoperatively. There was no relationship between changes in sinus function and changes in blood pressure over the 6 months period. Thus, carotid endarterectomy has no long-term hypotensive effect.

Carotid artery stenting and endarterectomy have different effects on heart rate variability

Objective Due to their close proximity to the carotid sinus baroreceptor region, carotid endarterectomy (CEA) and carotid angioplasty/stenting (CAS) carry an inherent risk of affecting baroreflex-mediated regulation of the heart rate. Variations in the heart rate can be studied by measuring heart rate variability (HRV), in which distinct frequency bands in the power spectrum represent sympathetic and parasympathetic modulations on sinus node pacemaker activity. We aimed to investigate the influence of CEA and CAS on HRV. Methods One-hour recordings of R–R intervals on ECG were obtained before and after CEA (10 patients) or CAS (12 patients). The power spectrum of the R–R time series was estimated using the FFT technique. The power in low frequency (LF) and high frequency (HF) bands were computed and normalized to their total power (TP). The LF / HF ratio, an index of sympathovagal balance, was calculated. Results Compared to preoperative levels, LF / HF exhibited 85%, 96%, and 70% increase on the second, third, and fourth days after CEA, respectively. In contrast, LF / HF decreased by 26%, 32%, and 26% on the respective days following CAS; the difference between groups was significant ( p = 0.0069). Normalized LF increased after CEA and decreased after CAS, while the opposite was observed for normalized HF ( p = 0.0217). There was no significant change in TP. Conclusions CEA and CAS have differential effects on the sympathovagal balance on the heart. The relative increase in sympathetic modulation after CEA and parasympathetic modulation after CAS are likely mediated by alterations in the sensitivity of carotid sinus baroreceptors. Altered cardiac autonomic modulation may play a role in the occurrence of cardiac disturbances following carotid interventions.

Exposure to a moderate intensity static magnetic field enhances the hypotensive effect of a calcium channel blocker in spontaneously hypertensive rats

We investigated the combined effects of a moderate intensity static magnetic field (SMF) and an L-type voltage-gated Ca(2+) channel blocker, nicardipine in stroke-resistant spontaneously hypertensive rats during the development of hypertension. Five-week-old male rats were exposed to SMF intensity up to 180 mT (B(max)) with a peak spatial gradient of 133 mT/mm for 14 weeks. Four experimental groups of 14 animals each were examined: (1) sham exposure with intraperitoneal (ip) saline injection (control); (2) SMF exposure with ip saline injection (SMF); (3) sham exposure with ip nicardipine injection (NIC); (4) SMF exposure with ip nicardipine injection (SMF + NIC). A disc-shaped permanent magnet or a dummy magnet was implanted in the vicinity adjacent to the left carotid sinus baroreceptor region in the neck of each rat. Nicardipine (2 mg/kg ip) was administered three times a week for 14 weeks, and then 15 min after each injection, arterial blood pressure (BP), heart rate (HR), baroreflex sensitivity (BRS), skin blood flow (SBF), skin blood velocity (SBV), plasma nitric oxide (NO) metabolites (NO(x) = NO(2) (-) + NO(3) (-)), plasma catecholamine levels and behavioral parameters of a functional observational battery were monitored. The action of nicardipine significantly decreased BP, and increased HR, SBF, SBV, plasma epinephrine and norepinephrine in the NIC group compared with the control respective age-matched group without changing plasma NO(x) levels. Neck exposure to SMF alone for 5-8 weeks significantly suppressed or retarded the development of hypertension together with increased BRS in SMF group. Furthermore, the exposure to SMF for 1-8 weeks significantly promoted the nicardipine-induced BP decrease in the SMF + NIC group compared with the respective NIC group. Moreover, the SMF induced a significant increase in plasma NO(x) in the nicardipine-induced hypotension. There were no significant differences in any of the physiological or behavioral parameters measured between the SMF + NIC and the NIC groups, nor between the SMF and the control groups. These results suggest that the SMF may enhance nicardipine-induced hypotension by more effectively antagonizing the Ca(2+) influx through the Ca(2+) channels compared with the NIC treatment alone. Furthermore, the enhanced antihypertensive effects of the SMF on the nicardipine-treated group appear to be partially related to the increased NO(x). Theoretical considerations suggest that the applied SMF (B(max) 40 mT, 0 Hz) can be converted into a changing magnetic field (B(max) 30-40 mT, 5.7-6.5 Hz or 7.5-8.3 Hz) in the baroreceptor region by means of the carotid artery pulsation. Therefore, we propose that the moderate intensity changing magnetic field, i.e., the magnetic field modulated by the pulse rate, may influence the activity of baroreceptor and baroreflex function.

Effects of neck exposure to 5.5 mT static magnetic field on pharmacologically modulated blood pressure in conscious rabbits

Static magnetic fields (SMF) in the millitesla (mT) range have been reported to modulate microcirculatory hemodynamics and/or blood pressure (BP) under pharmacologically modified state in mammals. This study was designed to investigate the acute effects of local application of a SMF to neck or pelvic region under pharmacologically modulated BP; norepinephrine (NE)-induced hypertension as well as an L-type voltage-gated Ca(2+) channel blocker, nicardipine (NIC)-induced hypotension in conscious rabbits. Magnetic flux densities were up to 5.5 mT and the spatial magnetic gradient peaked in neck (carotid sinus baroreceptor) region at the level of approximately 0.06 mT/mm. The duration of exposure was 30 min (including 10 min of pretreatment) and the effects on BP were investigated up to 100 min postexposure. Baroreflex sensitivity (BRS) was estimated from invasive recordings of systolic BP and pulse interval. Neck exposure to 5.5 mT significantly attenuated the pharmacologically induced vasoconstriction or vasodilation, and subsequently suppressed the increase or decrease in BP compared with sham exposure. In contrast, pelvic exposure to 5.5 mT did not significantly antagonized NE-elevated BP or NIC-reduced BP. The neck exposure to 5.5 mT has a biphasic and restorative effect on vascular tone and BP acting to normalize the tone and BP. The neck exposure to 5.5 mT caused a significant increase in BRS in NE-elevated BP compared with sham exposure. The buffering effects of the SMF on increased hemodynamic variability under NE-induced high vascular tone and NIC-induced low vascular tone might be, in part, dependent on baroreflex pathways, which could modulate NE-mediated response in conjunction with Ca(2+) dynamics.

Genistein inhibits carotid sinus baroreceptor activity in anesthetized male rats1

To study the effect of genistein (GST) on carotid baroreceptor activity (CBA). The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. GST at 50, 100, and 200 micromol/L inhibited the CBA, which shifted FCCB to the right and downward, with a marked decrease in peak slope and peak integral value of carotid sinus nerve discharge in a concentration-dependent manner. Pretreatment with 100 micromol/L NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, did not affect the effect of GST on CBA. Pretreatment with 500 nmol/L Bay K8644, an agonist of calcium channels, could completely abolish the effect of GST on CBA. A potent inhibitor of tyrosine phosphatase, sodium orthovanadate (1 mmol/L), could attenuate the inhibitory effect of GST. GST inhibits CBA, and the effect may be mediated by protein tyrosine kinase inhibition and a decrease in Ca2+ influx through the stretch-activated channels.

Doxapram inhibits carotid sinus baroreceptors in rabbits

1 To clarify the effects of doxapram on the baroreflex, we recorded carotid sinus nerve (CSN) activity in isolated and perfused carotid artery bifurcations of rabbits. 2 The CSN activity due to chemoreceptor stimulation was blocked by resection of the nerve branches from the carotid body. After the resection, the CSN activity was correlated to increase of carotid sinus (CS) pressure. 3 Administration of doxapram reduced the CSN activity originating from baroreceptors. The effect of doxapram on baroreceptors was dose dependent and reversible. 4 It is unlikely that doxapram altered CS wall mechanics because CS pressure did not change in the presence of the drug. 5 We conclude that doxapram acts on the cardiovascular system in part by inhibiting the negative feedback loop that originates in CS baroreceptors.

Dynamic Characteristics of Carotid Sinus Pressure-Nerve Activity Transduction in Rabbits

The dynamic characteristics of the baroreflex neural arc from pressure input to efferent sympathetic nerve activity (SNA) reveal derivative characteristics in the frequency range of 0.01 to 0.8 Hz (i.e., the baroreflex gain augments with increasing frequency) and high-cut characteristics in the frequency range above 0.8 Hz (i.e., the baroreflex gain decreases with increasing frequency) in rabbits. The derivative characteristics accelerate the arterial pressure regulation via the baroreflex. The high-cut characteristics preserve the baroreflex gain against pulsatile pressure by attenuating the high-frequency components less necessary for arterial pressure regulation. However, to what extent the carotid sinus baroreceptor transduction from pressure input to afferent baroreceptor nerve activity (BNA) contributes to these characteristics remains unanswered. To test the hypothesis that the carotid sinus pressure-BNA transduction partly explains the derivative characteristics but not the highcut characteristics, we examined the dynamic BNA response to pressure input in the frequency range from 0.01 to 3 Hz by using a white noise analysis in 7 anesthetized rabbits. The transfer function from pressure input to BNA showed slight derivative characteristics in the frequency range from 0.01 to 0.3 Hz with approximately a 1.7-fold increase in dynamic gain, but it showed no high-cut characteristics. In conclusion, the carotid sinus baroreceptor transduction partly explained the derivative characteristics but not the high-cut characteristics of the baroreflex neural arc. The present results suggest the importance of the central processing from BNA to efferent SNA to account for the overall dynamic characteristics of the baroreflex neural arc.

Arterial baroreflexes can determine long‐termblood pressure

Arterial baroreflexes can determine long‐termblood pressure

Cardiovascular responses to stress after carotid baroreceptor denervation in humans.

Iatrogenic bilateral denervation of carotid sinus baroreceptors may occur as a complication of carotid body tumor resection and radiation therapy of the neck. The acute phase of the resulting syndrome of baroreflex failure is characterized by a limited blood pressure buffering capacity against excessive rise or fall in response to emotional and physical stimuli like sexual arousal and cold. Paroxysms of severe hypertension and tachycardia, accompanied by excessive increments in sympathetic tone and catecholamine plasma levels, were ascribed to loss of tonic inhibitory influence of baroreceptors on sympathetic tone. Bilateral anesthetic blockade of baroreceptor afferent nerves was shown to result in a strong increase in muscle sympathetic nerve activity and disruption of its normal patterning. This chapter reviews our findings on the long-term effects of iatrogenic baroreflex trauma on the hemodynamic responses to pharmacological, physical, and emotional stress in the autonomic function laboratory as well as under daily life conditions. Chronic attenuation of baroreflex sensitivity after carotid body tumor resection and neck irradiation results in an increased blood pressure variability. However, unopposed sympathetic activation in response to physical and emotional stress appears to be limited to the acute phase of baroreflex failure.

NTS neuronal response to conversion from pulsatile to nonpulsatile pressure in isolated carotid sinus baroreceptors.

The purpose of this study was to demonstrate the effect of pulsatile pressure (PP) and nonpulsatile pressure (NP) on the carotid sinus baroreceptors and baroreceptor-related neurons in the nucleus tractus solitarius (NTS), using an isolated carotid sinus preparation in anesthetized rats. The baroreceptor activities were recorded from the carotid sinus nerves (CSN). Fifteen baroreceptor-related NTS neurons were recorded extracellularly. Conversion of PP to NP corresponded to a shift from phasic to irregular activity in the CSN and caused an increase in CSN activity at a mean pressure of 100 mm Hg. Under this condition, however, the discharge rate of baroreceptor-related NTS neurons was decreased and the systemic blood pressure was elevated. These results indicate that the increasing baroreceptor afferent input resulting from depulsation was not faithfully transmitted in the NTS, and suggest that the NTS is an important site for modifying the arterial baroreflex under NP.

Dynamics of sympathetic baroreflex control of arterial pressure in rats.

By a white noise approach, we characterized the dynamics of the sympathetic baroreflex system in 11 halothane-anesthetized rats. We measured sympathetic nerve activity (SNA) and systemic arterial pressure (SAP), while carotid sinus baroreceptor pressure (BRP) was altered randomly. We estimated the transfer functions from BRP to SNA (mechanoneural arc), from SNA to SAP (neuromechanical arc), and from BRP to SAP (total arc). The gain of the mechanoneural arc gradually increased about threefold as the frequency of BRP change increased from 0.01 to 0.8 Hz. In contrast, the gain of the neuromechanical arc rapidly decreased to 0.4% of the steady-state gain as the frequency increased from 0.01 to 1 Hz. Although the total arc also had low-pass characteristics, the rate of attenuation in its gain was significantly slower than that of the neuromechanical arc, reflecting the compensatory effect of the mechanoneural arc for the sluggish response of the neuromechanical arc. We conclude that the quantitative estimation of the baroreflex dynamics is vital for an integrative understanding of baroreflex function in rats.

Baroreflex control of muscle sympathetic nerve activity after carotid body tumor resection.

Bilateral carotid body tumor resection causes a permanent attenuation of vagal baroreflex sensitivity. We retrospectively examined the effects of bilateral carotid body tumor resection on the baroreflex control of sympathetic nerve traffic. Muscle sympathetic nerve activity was recorded in 5 patients after bilateral carotid body tumor resection (1 man and 4 women, 51+/-11 years) and 6 healthy control subjects (2 men and 4 women, 50+/-7 years). Baroreflex sensitivity was calculated from changes in R-R interval and muscle sympathetic nerve activity in response to bolus injections of phenylephrine and nitroprusside. In addition, sympathetic responses to the Valsalva maneuver and cold pressor test were measured. The integrated neurogram of patients and control subjects contained a similar pattern of pulse synchronous burst of nerve activity. Baroreflex control of both heart rate and sympathetic nerve activity were attenuated in patients as compared with control subjects [heart rate baroreflex sensitivity: 3.68+/-0.93 versus 11.61+/-4.72 ms/mm Hg (phenylephrine, P=0.011) and 2.53+/-1.36 versus 5.82+/-1.94 ms/mm Hg (nitroprusside, P=0.05); sympathetic baroreflex sensitivity: 3.70+/-2.90 versus 7.53+/-4.12 activity/100 beats/mm Hg (phenylephrine, P=0.10) and 3.93+/-4.43 versus 15.27+/-10.03 activity/100 beats/mm Hg (nitroprusside, P=0.028)]. The Valsalva maneuver elicited normal reflex changes in muscle sympathetic nerve activity, whereas heart rate responses were blunted in the patients with bilateral carotid body tumor resection. Maximal sympathetic responses to the cold pressor test did not differ between the two groups. Denervation of carotid sinus baroreceptors as the result of bilateral carotid body tumor resection produces chronic impairment of baroreflex control of both heart rate and sympathetic nerve activity. During the Valsalva maneuver, loss of carotid baroreflex control of heart rate is less well compensated for by the extra carotid baroreceptors than the control of muscle sympathetic nerve activity.

Carotid-sinus baroreflex modulation of core and skin temperatures in rats: an open-loop approach.

The neural mechanisms of the thermoregulatory control of core and skin temperatures in response to heat and cold stresses have been well clarified. However, it has been unclear whether baroreceptor reflexes are involved in the control of core and skin temperatures. To investigate how the arterial baroreceptor reflex modulates the body temperatures, we examined the effect of pressure changes of carotid sinus baroreceptors on core and skin temperatures in halothane-anesthetized rats. To open the baroreflex loop and control arterial baroreceptor pressure (BRP), we cut vagal and aortic depressor nerves and isolated carotid sinuses. We sequentially altered BRP in 20-mmHg increments from 60 to 180 mmHg and then in 20-mmHg decrements from 180 to 60 mmHg while measuring systemic arterial pressure (SAP), heart rate (HR), and core blood temperature (T(core)) at the aortic arch and skin temperature (T(skin)) at the tail. In response to the incremental change in BRP by 120 mmHg, SAP, HR, and T(core) fell by 90.3 +/- 5.1 mmHg, 60.3 +/- 10.5 beats min(-1), and 0.18 +/- 0.01 degrees C, respectively. T(skin) rose by 0.84 +/- 0.10 degrees C. The maximum rate of change per unit BRP change was -2.1 +/- 0.2 for SAP, -1.5 +/- 0.4 beats min(-1) mmHg(-1) for HR, -0.003 +/- 0.001 degrees C mmHg(-1) for T(core), and 0.011 +/- 0.002 degrees C mmHg(-1) for T(skin). After the administration of hexamethonium or bretylium, these baroreflexogenic responses were completely abolished. We concluded that T(core) and T(skin) are modulated by the arterial baroreceptor reflex.

Substance P release in the feline nucleus tractus solitarius during ergoreceptor but not baroreceptor afferent signaling

Substance P (SP) is associated with metabo- and mechanoreceptor afferent fibers (‘ergoreceptors’) in skeletal muscle as well as the afferent fibers from carotid sinus baroreceptors. Afferent activity from each of these are at least partially integrated in the nucleus tractus solitarius (NTS). The purpose of this study was to determine whether SP was released from the NTS during acute reflex-induced changes in blood pressure caused by stimulating these receptors. Both the muscle pressor response and the baroreflex were studied in adult cats anaesthetized with α-chloralose. SP antibody-coated microprobes were used to measure the possible release of SP from the NTS. The muscle pressor response caused a release of immunoreactive SP-like substances (irSP) from the rostral medial NTS, as well as the dorsal motor nucleus (DMV) and lateral tegmental field (FTL). This release was not dependent on intact afferent input from the carotid sinus nerve, but was a function of activation of muscle ergoreceptors, since no irSP was released in response to stimulation of the motor nerves after the muscle was paralyzed. There was no detectable release of irSP from the mNTS during carotid artery occlusions (baroreceptor unloading). Baroreceptor activation, induced by the i.v. injection of the vasoconstrictor, phenylephrine, did not cause the release of irSP from the mNTS above resting baseline levels. These data suggest that SP is involved with the mediation of the afferent signal from muscle ergoreceptor fibers in the medial NTS. SP is not involved with the mediation of baroreceptor afferent signaling in the medial NTS. The release of SP in response to ergoreceptors activation may function to excite an inhibitory pathway which inhibits baroreflex signals that would tend to reduce the blood pressure and heart rate during the muscle pressor response.

Noise-induced compensation for postural hypotension in primary autonomic failure

Noise can have a beneficial effect on sensory neurological systems, enhancing detection of small afferent signals and thereby improve efferent neural responses. We hypothesized whether a similar mechanism would facilitate impaired neural transmission associated with neurological disease, and tested whether addition of external noise to baroreceptor signaling could improve blunted autonomic efferent responses to a postural challenge in patients with primary autonomic failure (PAF). Five PAF patients were tested, one in duplicate and another triplicate, for their transient responses of heart rate (measured from electrocardiographic RR intervals; RRIs) and systolic (SBP) and diastolic (DBP) blood pressures to either 30° or 60° head-up tilt, with and without continuous application of beat-to-beat Gaussian white noise to the carotid sinus baroreceptors. Also, the effects of noise were compared with those by a continuous positive pressure applied to the carotid sinus baroreceptors. The data were fit to a first order model to evaluate the speed (by the time constant; τ) and the magnitudes (by the steady state gains; Gs) of RRI and blood pressure responses. The PAF patients exhibited marked drops in SBP and DBP and a blunted increase in heart rate upon transition from a supine to a head-up position. Addition of noise, not the continuous positive pressure, to the arterial baroreceptors significantly ( P<0.05) increased the G in RRI and diminished the Gs in SBP and DBP, though the time courses ( τs) of both the RRI and blood pressure responses were unaffected. The addition of external noise to baroreceptor signaling ameliorated the marked postural hypotension seen in patients with PAF.

Gender differences in carotid sinus baroreceptor reflexes in healthy young normal subjects and in ASCOT patients with treated essential hypertension

Gender differences in carotid sinus baroreceptor reflexes in healthy young normal subjects and in ASCOT patients with treated essential hypertension

Long-term effects of carotid sinus denervation on arterial blood pressure in humans.

After experimental carotid sinus denervation in animals, blood pressure (BP) level and variability increase markedly but normalize to preoperative levels within 10 to 14 days. We investigated the course of arterial BP level and variability after bilateral denervation of the carotid sinus baroreceptors in humans. We studied 4 women (age 41 to 63 years) who were referred for evaluation of arterial baroreflex function because of clinical suspicion of carotid sinus denervation attributable to bilateral carotid body tumor resection. The course of BP level and variability was assessed from repeated office and 24-hour ambulatory measurements (Spacelabs/Portapres) during 1 to 10 years of (retrospective) follow-up. Rapid cardiovascular reflex adjustments to active standing and Valsalva's maneuver were assessed. Office BP level increased from 132/86 mm Hg (range, 118 to 148/80 to 92 mm Hg) before bilateral surgery to 160/105 mm Hg (range, 143 to 194/90 to 116 mm Hg) 1 to 10 years after surgery. During continuous 24-hour noninvasive BP recording (Portapres), a marked BP variability was apparent in all 4 patients. Initial symptomatic hypotension on change to the upright posture and abnormal responses to Valsalva's maneuver were observed. Acute carotid sinus denervation, as a result of bilateral carotid body tumor resection, has a long-term effect on the level, variability, and rapid reflex control of arterial BP. Therefore, in contrast to earlier experimental observations, the compensatory ability of the baroreceptor areas outside the carotid sinus seems to be of limited importance in the regulation of BP in humans.

Right prefrontal activation produced by arterial baroreceptor stimulation: a PET study.

This study was performed to test the hypothesis of greater right hemispheric involvement in the processing of baroreceptor stimuli. Carotid sinus baroreceptors were stimulated by rhythmically decreasing air pressure in a neck chamber, and under control conditions the thorax was stimulated in a similar manner. Changes in regional cerebral blood flow (rCBF) were measured by PET. Baroreceptor stimulation resulted in rCBF increase in the right anterior-inferior prefrontal cortex (Brodmann areas (BA) 10/44/47) and bilaterally in BA 6/8. We conclude that in at least some stages of baroreceptor information processing the right hemisphere plays a greater role than the left hemisphere.

Noise-enhanced heart rate and sympathetic nerve responses to oscillatory lower body negative pressure in humans.

By injecting noise into the carotid sinus baroreceptors, we previously showed that heart rate (HR) responses to weak oscillatory tilt were enhanced via a mechanism known as "stochastic resonance." It remains unclear, however, whether the same responses would be observed when using oscillatory lower body negative pressure (LBNP), which would unload the cardiopulmonary baroreceptors with physically negligible effects on the arterial system. Also, the vasomotor sympathetic activity directly controlling peripheral resistance against hypotensive stimuli was not observed. We therefore investigated the effects of weak (0 to approximately -10 mmHg) oscillatory (0.03 Hz) LBNP on HR and muscle sympathetic nerve activity (MSNA) while adding incremental noise to the carotid sinus baroreceptors via a pneumatic neck chamber. The signal-to-noise ratio of HR, cardiac interbeat interval, and total MSNA were all significantly improved by increasing noise intensity, while there was no significant change in the arterial blood pressure in synchronized with the oscillatory LBNP. We conclude that the stochastic resonance, affecting both HR and MSNA, results from the interaction of noise with the signal in the brain stem, where the neuronal inputs from the arterial and cardiopulmonary baroreceptors first come together in the nucleus tractus solitarius. Also, these results indicate that the noise could induce functional improvement in human blood pressure regulatory system in overcoming given hypotensive stimuli.

Modulation of the carotid baroreceptor reflex by substance P in the nucleus tractus solitarius

Previous studies have shown that administration of substance P (SP) into the nucleus tractus solitarius (NTS) can evoke a depressor response similar to that produced by activation of the arterial baroreceptors. In addition, some studies have suggested that SP increases the reflex responses to activation of baroreceptor input. The present study was performed to determine the effects of SP on the carotid sinus baroreceptor reflex at the level of the NTS by examining the effects of both exogenous SP microinjected into different rostrocaudal locations in the NTS and blockade of the effects of endogenous SP, through the microinjection of a substance P antagonist (SPa; [ d-Pro, d-Trp]-substance P). Changes in pressure in an isolated carotid sinus in anesthetized dogs were used to evoke baroreflex changes in arterial blood pressure (BP) before and after microinjection of SP (0.5 μM) or SPa (10 μM) into barosensitive regions of the NTS. Microinjection of SP or its antagonist did not alter baseline, resting BP but did produce significant changes in baroreflex sensitivity. Microinjection of SP into different rostrocaudal regions of the NTS produced different responses, with rostral and caudal NTS microinjections producing significant increases in sensitivity. No effects on baroreflex sensitivity were obtained in response to SP microinjections into the intermediate NTS. Unlike SP, microinjection of the SPa significantly decreased baroreflex sensitivity at all rostrocaudal levels of the NTS. These data demonstrated that SP has the capability to modulate the carotid baroreflex at the level of the NTS and support a physiological role for endogenously released SP.