Baroreceptor Research Articles

Blood pressure and heart rate responses to sudden changes of gravity during exercise

Heart rate (HR) and blood pressure responses to sudden changes of gravity during 80- to 100-W leg exercise were studied. One group was exposed to sudden changes between 1.0 and 0 g in the head-to-foot direction (Gz+), starting upright and with repeated 30-s tilts to the supine position. Another group was exposed to sudden Gz+ changes between 1.8 and 0 g in an aircraft performing parabolic flight. Arterial blood pressure at the level of the carotid (carotid distending pressure, CDP) showed a large transient increase by 27-47 mmHg when Gz+ was suddenly decreased and a similar drop when Gz+ was suddenly increased. HR displayed a reverse pattern with larger transients (-22 to -26 min-1) in response to Gz+ decreases and more sluggish changes of lower amplitude in the other direction. Central blood volume, as estimated from the inverse of transthoracic impedance (1/TTI), varied in concert with Gz+. A model is proposed in which HR responses are described as a function of CDP and 1/TTI after a time delay of 2.3-3.0 s and including a low-pass filter function with time constants of 0.34-0.35 s for decreasing HR and time constants of 2.9-4.6 s for increasing HR. The sensitivity of the carotid component was around -0.8 to -1.0 min-1 . mmHg-1 (4-7 ms/mmHg). The cardiopulmonary baroreceptor component was an additive input but was of modest relative importance during the initial HR responses. For steady-state HR responses, however, our model suggests that inputs from carotid and cardiopulmonary receptors are of equal importance.

Reflex vascular responses from aortic arch, carotid sinus and coronary baroreceptors in the anaesthetized dog.

In chloralose-anaesthetized dogs, pressure applied to coronary, carotid and aortic baroreceptors were changed independently and the resulting reflex vascular responses were determined. Increases in pressure to each group of baroreceptors resulted in reflex vasodilatation; the maximal responses to distension of carotid and coronary baroreceptors were significantly larger than those to aortic receptors, but not different from each other. Increases in pressure in all three regions induced maximal responses at similar times from the onset of the pressure stimulus. However, the time for recovery of vascular resistance following a decrease in baroreceptor pressure differed. Vasoconstriction following a period of coronary hypertension occurred slowly, requiring 70 s for 90% of the response to develop. This was significantly longer than the corresponding times for carotid and aortic receptors (about 28 s). The rate of vasoconstriction in response to coronary baroreceptor unloading was influenced by the period for which the pressure stimulus was applied and vasoconstriction was even slower when the pressure stimulus had been maintained for 8 min. The mechanism responsible for delaying the vasoconstriction following a period of coronary hypertension is not known, but this effect may have important implications for the control of arterial blood pressure.

Transfer function analysis of central arc of aortic baroreceptor reflex in rabbits.

While electrically stimulating the aortic depressor nerve (ADN) pseudorandomly, we recorded renal sympathetic nerve activity (RSNA) and systemic arterial pressure (SAP) in 19 alpha-chloralose-anesthetized rabbits with sinoaortic denervation. From the recorded signals, we determined the transfer functions from ADN stimulation by a pseudorandom binary sequence to RSNA [HCMD.RSNA(f)] and to SAP [HCMD.SAP(f)]. The modulus of HCMD.RSNA(f) was flat over 0.0122-0.8 Hz, whereas the phase lag increased linearly with frequency. Thus the central transduction appeared not to modify the relative amplitude of the signals from the baroreflex afferents but to provide a fixed time delay (approximately 400 ms). In contrast, the modulus of HCMD.SAP(f) decreased precipitously toward high frequencies, and the degree of the phase lag was larger than that of HCMD.RSNA(f). We conclude that 1) the transfer property of the central are does not significantly modify the relative amplitude of the frequency components of the baroreflex afferents but provides a fixed time delay and 2) the frequency independence of the modulus of the transfer property is not preserved when the analysis is extended to SAP.

CNS pathways mediating cardiovascular regulation of vasopressin.

1. The release of vasopressin from the neurohypophysial terminals of hypothalamic magnocellular neurosecretory neurons is subject to regulation by peripheral baroreceptors, cardiopulmonary volume receptors and circulating angiotensin II. Information from these sources is transmitted through different pathways to achieve different influences on the excitability of the vasopressin-secreting cells. 2. A brief increase in arterial pressure, sufficient to activate baroreceptors, is associated with a transient and selective GABAergic inhibition of these neurosecretory neurons, achieved through a multisynaptic pathway that involves ascending catecholaminergic fibres and neurons in the diagonal band of Broca. A decrease in arterial pressure activates peripheral low volume receptors and initiating neural inputs that result in an increase in the excitability of vasopressin-secreting neurons, achieved via pathways that include direct projections from caudal ventrolateral medulla A1 neurons. 3. Hypotension also releases renal renin and leads to the formation of angiotensin II; binding of this hormone to AT1 receptors on subfornical organ neurons promotes activation of a central angiotensinergic input that evokes a predominantly excitatory effect on vasopressin neurons.

Effects of intravenous mepivacaine on renal sympathetic nerve activity in the cat during nitrous oxide and nitrous oxide-halothane anesthesia.

Because hemodynamic responses to systemic mepivacaine may be influenced by sympathetic change and concurrent general anesthesia, the authors directly measured renal sympathetic nerve activity (RSNA) during intravenous administration of mepivacaine in subseizure through seizure doses under N2O-O2 and N2O-O2-halothane anesthesia. Thirty-four cats were randomly assigned to five groups. Groups I-A, I-B, and I-C received incremental subseizure doses of intravenous mepivacaine (2 mg/kg, 5 mg/kg, and 10 mg/kg). Groups II-A and II-B received intravenous infusion of mepivacaine (4 mg/kg/min). Anesthesia was maintained with N2O(70%)-O2 in groups I-A, I-C, and II-A, and with N2O(70%)-O2-halothane (1%) in groups I-B and II-B. Cats in group I-C had undergone total baroreceptor denervation. Heart rate (HR), mean arterial pressure (MAP), and RSNA were measured. In group I-A, MAP did not significantly change with intravenous mepivacaine, though RSNA and HR significantly decreased (P < .05) respectively with 5 mg/kg i.v. and 10 mg/kg i.v. mepivacaine. In group I-C, HR, MAP, and RSNA did not change significantly. In group I-B, HR and MAP decreased with bolus intravenous doses of mepivacaine in a dose-dependent fashion, but RSNA did not change significantly. All cats in group II-A developed seizure by mepivacaine infusion at mean total dose of 28.9 +/- 4.2 mg/kg without significant changes in HR, MAP, or RSNA. In group II-B, mepivacaine infusion resulted in circulatory collapse at mean total dose of 34.3 +/- 4.6 mg/kg without seizure or significant RSNA change. The authors conclude that intravenous mepivacaine induces occasional depression in HR and RSNA during N2O-O2 anesthesia, but in addition induces dose-related circulatory depression during N2O-O2-halothane anesthesia via nonsympathetic mechanism(s).

Modifications induced by -10 degrees Trendelenburg's posture in sodium tubular handling in patients with essential hypertension.

In essential hypertensive patients "exaggerated natriuresis" is a response to acute volume expansion. However, the underlying mechanisms for this remain to be determined. We studied 19 patients with essential hypertension (HP) and 9 normotensive subjects (NS). In all examined subjects the response to acute central volume expansion, without the plasma compositional change that Trendelenburg's position involves, was evaluated during 90 min (period T) after a similar period of deambulation (period D). Mean blood pressure (MBP), tubular sodium handling by the lithium clearance technique, plasma renin activity (PRA), plasma aldosterone (PA), plasma catecholamines and urine prostaglandine E2 and kallikrein were assessed after D and T. MBP was significantly higher in HP than in NS (p = 0.00001). HP showed "exaggerated natriuresis" after T (fractional excretion of sodium increased from 0.55 +/- 0.1% after D to 1.20 +/- 0.2% after T, p < 0.01). This was because of a decrease in their proximal fractional reabsorption of sodium (from 74.96 +/- 1.8% after D to 62.50 +/- 2.8% after T, p < 0.01). Plasma epinephrine and plasma dopamine after T were significantly lower than in standing position in HP (p < 0.01) but no in NS. The decrease in plasma renin activity after T in HP was 53%, and 32% in NS. There were not any significant differences between groups in the other neurohormonal systems studied. We conclude that the major determinant of "exaggerated natriuresis" in hypertensive patients is a higher stimulation of the cardiopulmonary receptors following Trendelenburg's position and consequently stronger reflex inhibition of sympathetic system activity and renin-angiotensin II activity. The "exaggerated natriuresis" after Trendelenburg's position in HP was an expression of abnormal pressure natriuresis.

Cardiovascular and respiratory changes following exposure to a synthetic toxin of

The present study demonstrated cardiorespiratory effects of a synthetic phosphorus-containing ichthyotoxic metabolite elaborated by the marine dinoflagellate Ptychodiscus brevis in anaesthetised cats. The metabolite at a dose of 0.25–1.5 mg/kg i.v., resulted in a dose-dependent fall in blood pressure and such vasodepressor effect was associated with bradycardia. There is initial respiratory apnoea ollowed by increased rate and depth of respiration (hyperapnoea) following the administration of the toxin. The hypotensive response was accompanied by a decrease in aortic baroreceptor activity. The ECG showed atrioventricular conduction block, arrhythmia and depression of S-T segment and T wave which indicated coronary insufficiency. Vasodepressive property of the toxin is presumably muscarinic in nature as atropine counteracted the vasodepression.

Convergence of ventrolateral medulla and aortic baroreceptor inputs onto amygdala neurons

Experiments were done to investigate the effect of stimulation of neurons in ventrolateral medulla (VLM) and aortic baroreceptors on the discharge rate of amygdala neurons. The region of central nucleus of the amygdala (ACe) was explored for spontaneously active single units that altered their discharge rate to electrical stimulation of VLM in the α-chloralose anesthetized rat. Responsive units were also assessed for their response to electrical stimulation of the aortic depressor nerve (ADN). Stimulation of VLM altered the discharge rate of 47% (43/92) of the units tested in and around the region of ACe. Of these units, 60% (26/43) were excited (mean latency 13.6 ± 3.6 ms) and 40% (17/43) were inhibited (mean latency, 23.1 ± 4.3 ms) by VLM stimulation. Of the 43 units that responded to stimulation of VLM, 19 (44%) also responded to ADN stimulation with a mean latency of 32.5 ± 7.6 ms. These data demonstrate that inputs from VLM and ADN converge onto ACe neurons and suggest that VLM may function as a relay for cardiovascular afferent information to the amygdala.

Ionic and haemodynamic changes influence the release of the excitatory amino acid glutamate in the posterior hypothalamus.

The push-pull technique was used to investigate the release of the excitatory amino acid glutamate in the posterior hypothalamic area of the conscious rat. The hypothalamus was superfused through the push-pull cannula with artificial cerebrospinal fluid (CSF), and the superfusate was collected in time periods of 10 min when ionic conditions in the CSF were changed, or in short periods of 3 min when blood pressure changes were evoked. The mean glutamate release rate was 2.8 +/- 0.7 pmol/min. Depolarization by hypothalamic superfusion with CSF containing 50 mM K+ enhanced the release of glutamate in the presence of Ca2+. The K(+)-induced release was attenuated by 40% when the hypothalamus was superfused with Ca(2+)-free CSF. Replacement of Ca2+ by Mg2+ abolished the K(+)-induced release of glutamate. Hypovolaemia elicited by haemorrhage enhanced the release rate of glutamate. Similarly, a hypotension elicited by i.v. injection of chlorisondamine (3 mg/kg) led to a pronounced and permanent enhancement in glutamate release. The effects of hypovolaemia and chlorisondamine on glutamate release were abolished in aortic denervated rats, indicating that this response is due to a decrease of impulse generation in baroreceptors. A hypervolaemia elicited by blood infusion did not affect the release of glutamate. Similarly, a pronounced pressor response to phenylephrine (15 micrograms/kg per minute) infused intravenously for 9 min was ineffective. The results show that the K(+)-induced release of glutamate in the hypothalamus is dependent on the presence of Ca2+. The increase in glutamate release rate by hypovolaemia or chlorisondamine suggests that the glutamatergic neurons in the posterior hypothalamic area respond to unloading of aortic baroreceptors and possess a counteracting, hypertensive function.

Cardiovascular and respiratory changes following exposure to a synthetic toxin of Ptychodiscus brevis

The present study demonstrated cardiorespiratory effects of a synthetic phosphorus-containing ichthyotoxic metabolite elaborated by the marine dinoflagellate Ptychodiscus brevis in anaesthetised cats. The metabolite at a dose of 0.25–1.5 mg/kg i.v., resulted in a dose-dependent fall in blood pressure and such vasodepressor effect was associated with bradycardia. There is initial respiratory apnoea ollowed by increased rate and depth of respiration (hyperapnoea) following the administration of the toxin. The hypotensive response was accompanied by a decrease in aortic baroreceptor activity. The ECG showed atrioventricular conduction block, arrhythmia and depression of S-T segment and T wave which indicated coronary insufficiency. Vasodepressive property of the toxin is presumably muscarinic in nature as atropine counteracted the vasodepression.

Baroreceptors in the carotid sinus contribute to arterial baroreceptor reflexes in normotensive rats.

1. Baroreceptor reflex influences on renal sympathetic nerve activity (RSNA) were estimated with non-linear regression analysis (sigmoidal curve fitting) before and after transection of carotid sinus nerves (CSN) and aortic depressor nerves (ADN) in rats. 2. Transection of ADN reduced the gain of the reflex to 42% of basal levels with increases in arterial pressure (MAP) and RSNA. Subsequent transection of CSN eliminated the remaining sigmoidal correlation between MAP and RSNA without further changes in resting MAP and RSNA. 3. By comparison, the transection of CSN reduced the gain of the reflex to 53% of basal levels without affecting other variables. Additional transection of both ADN eliminated the remaining sigmoidal correlation between MAP and RSNA with further increases in resting MAP and RSNA. 4. These results indicate that carotid sinus baroreceptors exist in rats. They contribute to baroreceptor-mediated reflex changes in RSNA as do aortic baroreceptors, although the working range of MAP may increase with transection of the latter.

Abnormalites of autonomic nervous system in hyperadrenergic orthostatic hypotension: Description of a case

Hyperadrenergic orthostatic hypotension was diagnosed in a 27-year-old man because of recurrent episodes of hypotension associated with high plasma noradrenaline levels. In this patient, laboratory tests were performed to evaluate autonomic nervous system function. Decreased response to Valsalva maneuver and carotid sinus massage indicated decreased baroreflex and vagal responsiveness, respectively. Cardiovascular response to the handgrip was reduced in comparison to controls. Passive leg raise showed normal reduction of plasma norepinephrine, indicating normal responsiveness of cardiopulmonary receptors. ‘Non-dipper’ profile in the ambulatory blood pressure monitoring provided further evidence for an impaired autonomic control of cardiovascular function in this patient. This report suggests the presence of autonomic dysfunction in hyperadrenergic orthostatic hypotension.

‘Aortic baroreceptor’ neurons in the nucleus tractus solitarius in rats: Convergence of cardiovascular inputs as revealed by heartbeat-locked activity

Rat aortic depressor nerve (ADN) contains only baroreceptor afferents. We identified ‘aortic baroreceptor’ neurons in the nucleus tractus solitarius (NTS) as those responding to electrical stimulation of the ADN and attempted to demonstrate convergence of cardiovascular mechanoreceptor inputs in these ‘baroreceptor’ neurons. In chloralose-urethane-anesthetized rats, ADN stimulation evoked either short or long latency responses (SLR, LLR) in 193 neurons of the NTS. 28 (SLR, 15; LLR, 13) demonstrated ongoing activities with cardiac rhythm despite the fact that the ADN had been cut peripherally. In 12 (SLR, 5; LLR, 7) of the 28 neurons, heartbeat-locked activity was abolished by carotid occlusion (CO), and augmented by methoxamine-induced blood pressure elevation, indicating that the heartbeat-locked activity originated from carotid sinus baroreceptors (CSB). In 11 neurons (SLR, 6; LLR, 5), the heartbeat-locked activity was not affected by CO but was abolished by topical application of lidocain on the ipsilateral cervical vagus, suggesting that the heartbeat-locked activity originated mostly from cardiac mechanoreceptors. The origin of the heartbeat-locked activity of the remaining 5 neurons could not be determined. The onsets, as well as peaks of the heartbeat-locked activity of vagal origin appeared significantly earlier than those of CSB origin. In conclusion, NTS neurons receive converging projectinn not only from the two major arterial baroreceptors but also from the arterial baroreceptors and cardiac mechanoreceptors, thereby integrating sensory information of vascular and cardiac origins.

Dynamics of sensory afferent synaptic transmission in aortic baroreceptor regions on nucleus tractus solitarius.

1. Synaptic responses of medial nucleus tractus solitarius (mNTS) neurons to solitary tract (ST) activation were studied in a horizontal brain slice preparation of the rat medulla. Slices included sections of ST sufficiently long that the ST could be electrically activated several millimeters from the recording site of cell bodies in mNTS. 2. Three types of synaptic events were evoked in response to ST stimulation: simple excitatory postsynaptic potentials (EPSPs), simple inhibitory postsynaptic potentials (IPSPs), and complex EPSP-IPSP sequences. Simple EPSPs had substantially shorter latencies than IPSPs (3.39 +/- 0.65 ms, mean +/- SE, n = 42, vs. 5.86 +/- 0.71 ms, n = 6, respectively). 3. EPSP amplitude increased linearly with increasing hyperpolarization, with an extrapolated reversal potential near 0 mV. 4. EPSPs were maximal at < 0.5 Hz of sustained, constant-frequency ST stimulation (n = 14). EPSP amplitude declined to an average of 57.5% of control at 10 Hz after 2 s of sustained stimulation. With 1 min of sustained, 100-Hz stimulation, EPSP amplitude declined to near zero. 5. With stimuli intermittently delivered as 100-ms bursts every 300 ms, generally comparable average EPSPs were evoked during constant and burst patterns of ST stimulation. The amplitude of the initial EPSP in each burst was very well maintained even at intraburst stimulation rates of 100 Hz. 6. At resting membrane potentials, low constant frequencies of ST stimulation (< 5 Hz) reliably elicited action potentials and suppressed spontaneous spiking, but higher frequencies led to spike failures (> 85% at 100 Hz). Between 5 and 10 Hz, this periodic stimulation-suppression cycle clearly entrained action potential activity to the ST stimuli. Similar patterns of current pulses (5 ms) reliably evoked action potentials with each pulse to higher frequencies (50 Hz) without failures, and entrainment was similar to ST stimulation. 7. In a subset of nucleus tractus solitarius (NTS) neurons (3 of 9 studied), bursts of ST stimuli were as much as 50% more effective at transmitting high frequencies (> 10 Hz) of ST stimulation than the equivalent constant frequencies (P < 0.0001). 8. The long-latency simple IPSPs with no preceding EPSPs reversed to become depolarizing at potentials more negative than -62.9 +/- 7.0 mV (n = 5) and were blocked by the non-N-methyl-D-aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (n = 3). The ST stimulation frequency-response relation of these IPSPs was similar to that for the short-latency EPSP response excited by ST synapses. Thus these IPSPs appear to be activated polysynaptically via a glutamatergic-GABAergic sequence in response to ST activation. 9. The results suggest that sensory afferent synapses in mNTS have limited transmission of high-frequency inputs. Both synaptic transmission and the characteristics of the postsynaptic neuron importantly contribute to the action potential transmission from afferent to NTS neuron and beyond. This overall frequency response limitation may contribute to the accommodation of reflex responses from sensory afferent inputs such as arterial baroreceptors within their physiological discharge frequency range.

Enhanced cardiopulmonary reflex inhibition of heart rate during exercise

We tested the hypothesis that the reflex inhibition of heart rate (HR) during mechanical (acute bolus injection of 0.5% and 2% of estimated blood volume) and chemical (phenylbiguanide, PBG, 2.5 and 5 micrograms.kg-1) stimulation of cardiopulmonary receptors would be enhanced during exercise. Rats were instrumented with arterial and venous catheters. The reflex response to mechanical (N = 7) and chemical (N = 8) stimulation of cardiopulmonary receptors was examined at rest and during exercise (6 m.min-1, 10% grade). A two-way analysis of covariance (ANCOVA) with repeated measures was used to test for differences in the reflex regulation of HR at rest vs exercise. HR was used as the covariate because exercise significantly increased baseline HR. There was no significant treatment effect (rest vs exercise) for the reflex inhibition of HR during mechanical stimulation. However, the two-way ANCOVA revealed a significant treatment effect (rest vs exercise) for the reflex inhibition of HR during chemical stimulation. The reflex decreases in HR were enhanced (-delta 23 +/- 8 vs -delta 133 +/- 47 and -delta 208 +/- 40 vs -delta 374 +/- 10 bpm at 2.5 and 5 micrograms.kg-1, respectively). These data suggest that factors associated with exercise enhanced the cardiopulmonary reflex inhibition of heart rate during chemical stimulation.

Central blood volume influences sympathetic sudomotor nerve traffic in warm humans.

The objective of this study was to test whether changes in central blood volume can induce reflex effects on sweating. Multi-unit skin sympathetic nerve activity (SSA) was recorded from the posterior cutaneous nerve of the forearm or radial nerve branches in 11 healthy volunteers. Skin electrical resistance and skin blood flow were recorded in the area innervated by the impaled nerve fascicle. Sudomotor nerve traffic and sweating was induced by whole body heating. Lower body negative pressure (LBNP) and tilting (30 degrees head up) was used for blood volume displacement from the chest to the lower body. Low levels of LBNP (5 and 10 mmHg) had no effect on blood pressure, heart rate or skin blood flow but induced a prompt inhibition of SSA and a reduced number of transient skin resistance changes (n = 9), both rapidly returning to control levels after cessation of LBNP. Quantitatively, the effect was similar at both levels of LBNP. Head up tilting also reduced SSA (n = 3, 19 tilt manoeuvres). A capacity for mental stress-induced SSA increase remained during LBNP. Spontaneous fluctuations in blood pressure did not affect SSA, arguing against arterial (high-pressure) baroreceptors modulating SSA. Consequently, the present results indicate that unloading of cardiopulmonary (low-pressure) volume receptors reduces sympathetic sudomotor nerve traffic and sweating in warm subjects. It is suggested that the reflex contributes to counteracting hypovolaemia.

Differential Modulation of Baroreceptor Sensitivity by Long-term Antihypertensive Treatment

We investigated the effects of long-term oral treatment with four different classes of antihypertensive drugs (a thiazide diuretic [trichlormethiazide, 10 mg/kg per day]; a beta-blocker [atenolol, 90 mg/kg per day]; a calcium channel antagonist [nicardipine, 150 mg/kg per day]; and an angiotensin-converting enzyme inhibitor [enalapril maleate, 10 mg/kg per day]) on aortic baroreceptor activity in spontaneously hypertensive rats with chronic hypertension (36 weeks of age). Treatment with each of the four drugs, given from 10 to 36 weeks of age, similarly decreased arterial pressure (171 +/- 2 to 144 +/- 1 mm Hg, P < .01) and similarly decreased the threshold pressure for baroreceptors (116 +/- 3 to 103 +/- 1 mm Hg, P < .05). The four antihypertensive drugs also potentiated the maximal gain of the pressure-activity relation in these rats (untreated, 1.08 +/- 0.05% maximum/mm Hg); however, nicardipine and enalapril (1.77 +/- 0.04% and 1.70 +/- 0.06% maximum/mm Hg, respectively) augmented the maximal gain to a greater extent (P < .05 to .01) than did trichlormethiazide or atenolol (1.49 +/- 0.05% and 1.42 +/- 0.02% maximum/mm Hg, respectively). When the initiation of treatment was delayed to 28 weeks of age, no differences were found in the effects on either threshold pressure (104 +/- 1 mm Hg) or maximal gain (1.36 +/- 0.03% maximum/mm Hg) for all four drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Upregulation of imidazoline receptors in the medulla oblongata accounts for the enhanced hypotensive effect of clonidine in aortic barodenervated rats

The present study tested the hypothesis that an upregulation of the imidazoline receptor in the rostral ventrolateral medulla (RVLM) of aortic barodenervated (ABD) rats may account for the enhanced hypotensive effect of clonidine. In vitro autoradiographic radioligand binding studies were utilized to investigate the binding characteristics of imidazoline receptors in the RVLM and nucleus tractus solitarius (NTS), areas that play critical roles in cardiovascular regulation and elicitation of clonidine responses. ABD but not sham operation (SO) caused immediate and significant ( P < 0.05) increases in mean arterial pressure (MAP) and heart rate (HR) and an impairment of the baroreflex-mediated HR response (baroreflex sensitivity, BRS). Two days after ABD, these parameters, except BRS, subsided to near-control (SO) levels. Intracisternal (i.c.) administration of clonidine (0.1 μg) elicited a 3-fold greater decrease in BP of conscious ABD compared with SO rats (−20.3 ± 2.6 vs. −7.4 ± 0.9 mmHg) thus demonstrating the ability of ABD to enhance centrally-mediated hypotensive responses. Autoradiographic visualization of brain sections obtained from separate groups of ABD and SO rats 48 h after surgery preincubated with [ 3H]idazoxan (2.5–3.5 nM) showed that [ 3H]idazoxan binding in RVLM, middle NTM (mTNS) and rostral NTS (rNTS) was saturable and of high affinity. Uneven distribution of imidazoline binding sites was evident since in control (SO) rats, Scatchard analysis of binding data revealed similar densities ( B max) of [ 3H]idazoxan binding sites in the RVLM and mNTS versus significantly higher density in the rNTS. In ABD rats, the binding dissociation constant ( K d) was significantly decreased in both the RVLM (8.1 ± 3.1 vs. 21.4 ± 5.0 nM) and rNTS (12.3 ± 1.3 vs. 18.6 ± 3.1 nM) compared with SO rats while the B max was not affected. This finding suggests an increased receptor affinity in the RVLM and rNTS of barodenervated rats. The mNTS of ABD rats exhibited significant increases in the B max (861 ± 96 vs. 570 ± 87 fmol/mg protein) compared with values of SO rats but the receptor affinity was not affected. It is concluded that: (i) aortic baroreceptors exert a tonic inhibitory influence on central imidazoline receptor function; and (ii) the enhanced hypotensive effect of clonidine in conscious ABD rats may be accounted for by the increased affinity of the medullary imidazoline receptors particularly in the RVLM.

Effects of static lung inflation on sympathetic activity in human muscle nerves at rest and during asphyxia

Muscle sympathetic activity is inhibited during the second half of phasic lung inflation associated with normal (negative pressure) breathing or artificial ventilation with intermittent positive-pressure, and this inspiratory inhibition appears unrelated to the associated changes in arterial pressure. In the present study we tested the hypothesis that a static inflation of the lungs would cause a sustained inhibition of muscle sympathetic activity. Microneurographic techniques were used to record muscle sympathetic activity from the peroneal nerve, and arterial pressure was monitored continuously by finger-pulse photoplethysmography (Finapres). In nine subjects static lung inflation, brought about either actively or passively, caused a pronounced and sustained increase in sympathetic activity (not the predicted decrease) that could not be explained by changes in arterial pressure. When delivered at the end of a voluntary end-expiratory apnoea, static lung inflation caused an initial inhibition of the large chemoreceptor-induced sympathetic bursts and a subsequent excitation that was sustained for the duration of the lung inflation. These observations indicate that respiration can affect muscle sympathetic activity in humans in two opposing ways: inhibition during phasic increases in lung volume, and excitation during large static increases in lung volume. Neither phenomenon depends on changes in arterial pressure, and hence influences of carotid arterial and aortic (high-pressure) baroreceptors can be excluded. We suggest that the initial inhibition is evoked from lung or chest-wall receptors and the static exitation from unloading of cardiopulmonary (low pressure) baroreceptors.

Fos-determined distribution of neurons activated during the Bezold-Jarisch reflex in the medulla oblongata in conscious rabbits and rats

Experiments were performed in unanaesthetized rabbits and rats to investigate the distribution, within the medulla oblongata, of neurons activated during the Bezold-Jarisch reflex. Repeated intravenous injections of phenylbiguanide evoked depressor and bradycardic responses in both rabbits and rats. Fos-positive neurons were present in the nucleus tractus solitarius and in the caudal ventrolateral medulla oblongata. Double-label tyrosine hydroxylase (TH) immunohistochemical studies in the ventrolateral medulla showed that most Fos-positive neurons in the caudal ventrolateral medulla were TH-negative neurons scattered between A1 noradrenaline cells, in the rabbit and in the rat. Approximately 20% of neurons in the caudal ventrolateral medulla in rabbits, and 50% in rats, were immunoreactive for both Fos and TH. Some Fos-positive, TH-negative neurons in the caudal ventrolateral medullawere retrogradely labelled with cholera toxin B-Gold after injection of this tracer into the sympathoexcitatory region of the rostral ventrolateral medulla. Our data suggests that neurons in the nucleus tractus solitarius, and rostrally projecting TH-negative neurons in the caudal ventrolateral medulla, are part of the pathway by which stimulation of cardiopulmonary receptors inhibits sympathetic vasomotor tone to decrease blood pressure during the Bezold-Jarisch reflex.