Neck Chamber Research Articles

Influence of captopril on the arterial baroreceptor reflex in patients with heart failure.

In 16 male patients with heart failure (NYHA II-III), the influence of a single dose of 25 mg captopril on the carotid sinus baroreceptor reflex was examined. Blood pressure fell significantly by 11 +/- 1.7 mm Hg (P less than 0.001), whereas heart rate remained unchanged (85 +/- 3 vs. 83 +/- 3 beats min-1). Carotid sinus baroreceptors were stimulated by means of an airtight neck chamber. Two indices of baroreflex sensitivity were calculated. (1) The sensitivity to reflex heart rate slowing was increased by captopril from -2.9 +/- 0.7 to -5.0 +/- 1.3 ms mmHg-1 (P less than 0.02). The higher the initial sensitivity the more pronounced was the change after captopril with an increase of sensitivity by 46% (y = 1.46x -0.17, P less than 0.01). This increase in sensitivity cannot be explained by haemodynamic changes induced by captopril. (2) In eight patients the sensitivity of the baroreflex to increased transmural pressure gradients of the carotid sinus was evaluated by registration of the blood pressure response to neck suction; this demonstrated an unchanged responsiveness following captopril administration. From these data it can be concluded that captopril selectively augments a reflex bradycardia which is mediated by an increase in vagal efferent tone. The change in the reflex response depends on the initial reflex sensitivity and cannot be explained by haemodynamic changes caused by captopril.

Reduction of atrial natriuretic factor circulating levels by endogenous sympathetic activation in hypertensive patients.

The effects of endogenous activation of sympathetic nervous system on systemic and regional hemodynamics and on plasma levels of atrial natriuretic factor (ANF) were studied in subjects with essential hypertension. Stimulation of sympathetic nervous system was reflex-induced by a selective deactivation of carotid baroreceptors obtained by increasing external neck-tissue pressure (NTP) by means of a neck chamber. The effects of graded levels (+30, +45, and +60 mm Hg) and one single and sustained level (+45 mm Hg for 15 min) of NTP were studied. As expected, NTP caused reflex increases in blood pressure, heart rate, and forearm vascular resistance, whereas atrial pressures did not change significantly and cardiac output tended to increase. In the studies based on graded levels of NTP, immunoreactive ANF (irANF) progressively fell (from 31.7 +/- 10 to 13.3 +/- 4 fmol/ml; p less than .05) and the changes in irANF were significantly correlated with those observed in FVR (r = -.671, p less than .001). Both hemodynamic and irANF changes were prevented by adrenergic blockade (phentolamine + propranolol). During +45 mm Hg NTP for 15 min, the levels of irANF fell both in the pulmonary artery and in the inferior vena cava. The irANF arteriovenous difference also fell during this maneuver. These data show that, in hypertensive patients, factors other than atrial wall tension may influence ANF release. They also show that endogenous sympathetic activation may reduce ANF release.

Neural Control of Circulation Before and After Intravenous Urapidil in Essential Hypertension

Drugs interfering with sympathetic influences on the cardiovascular system have been shown to effectively lower blood pressure in hypertension. However, sympathetic cardiovascular control is involved in blood pressure homeostasis, which means that these drugs may produce potential adverse haemodynamic effects that may reduce the benefit of their antihypertensive action. This paper summarises the results of a study in which we examined the effects of urapidil on the arterial baroreflex and the cardiopulmonary reflex in 6 essential hypertensive patients given 25 mg of the drug intravenously. The dose of the drug used caused a marked reduction in arterial blood pressure (direct measurement). However, pressor and depressor responses to carotid baroreceptor deactivation and stimulation (neck chamber device), respectively, were not modified when compared with those observed in the placebo period. This was also the case for increases and reductions in both forearm vascular resistance and plasma noradrenaline (norepinephrine) concentrations induced by deactivating and stimulating cardiopulmonary receptors, respectively. The pressor and tachycardic responses to handgrip and cold exposure were also unaffected by the drug. It is concluded that when administered at a clinically effective dose urapidil does not adversely affect major reflex mechanisms involved in neural cardiovascular regulation. This has favourable implications for the use of the drug in clinical practice.

Isometric exercise modifies autonomic baroreflex responses in humans.

The influence of brief, moderate isometric exercise on the earliest vagal and sympathetic responses to changes of afferent carotid baroreceptor activity was studied in 10 healthy young men and women. Vagal-cardiac nerve activity was estimated from changes of electrocardiographic R-R intervals, and postganglionic peroneal nerve muscle sympathetic activity was measured directly from microneurographic recordings. Carotid baroreceptor activity was altered with 5-s periods of 30 Torr pressure or suction applied to a neck chamber during held expiration. Brief handgrip (30% of maximum) significantly reduced base-line R-R intervals, did not modify reductions of R-R intervals during neck pressure, and significantly reduced increases of R-R intervals during neck suction. Handgrip did not significantly increase base-line sympathetic activity from resting levels, but it significantly diminished increases of sympathetic activity during neck pressure and augmented reductions of sympathetic activity during neck suction. Our results suggest that exercise modifies, in small but significant ways, early sympathetic and vagal responses to abrupt changes of arterial baroreceptor input in humans.

Progressive attenuation of the carotid baroreflex control of blood pressure and heart rate during exercise

With the use of a variable pressure neck chamber, the effect of supine bicycle exercise on the carotid baroreceptor reflex was investigated in 10 normal volunteers who were studied at rest and during moderate and severe exercise, i.e., at 33% and 66% of their previously determined maximal exercise capacity. Deactivation of the carotid baroreceptors by a decrease in carotid transmural pressure produced a greater ( p < 0.001) increase in mean intra-arterial pressure at rest (+11.2 ± 0.2 [SE] mm Hg) than during moderate (+9.0 ± 0.2 mm Hg) and severe (+6.1 ± 0.1 mm Hg) exercise. Heart interval decreased less ( p < 0.005) at rest (−73 ± 3.2msec) than during exercise (−0.7 ± 0.7 msec and −4.6 ± 0.2 msec, respectively). Furthermore, activation of the carotid baroreceptors by an increase in carotid transmural pressure provoked a greater ( p < 0.005) reduction in mean intra-arterial pressure at rest (−11.5 ± 0.2 mm Hg) than during exercise (−9.8 ± 0.1 mm Hg and −7.5 ± 0.1 mm Hg, respectively), while the lengthening of heart interval was also more ( p < 0.005) pronounced at rest (+97 ± 4.3 msec) than during moderate (+44 ± 1.2 msec) and severe (+7.6 ± 0.3 msec) exercise. Finally, carotid baroreceptor sensitivity was defined as the slope of the changes in blood pressure and heart interval that occurred with increasing (baroreceptor deactivation) and decreasing (activation) neck tissue pressure. On average, baroreceptor sensitivity was consistently smaller ( p < 0.05) during exercise, as compared to rest. In conclusion, in humans the carotid baroreceptor reflex control of heart interval and blood pressure is progressively attenuated during dynamic exercise in the supine position.

Continuous resetting of the human carotid baroreceptor-cardiac reflex.

Although human baroreflex responses have been studied during night as well as day, there has been no attempt to distinguish circadian changes of baroreflex function from those related to sleep. We measured carotid baroreceptor-cardiac reflex responses serially during a 24-h period in 11 normotensive volunteers who were awake and cooperative during testing. We applied sequences of ramped R-wave-triggered neck chamber pressure changes from +40 to -65 mmHg, during held expiration, at 3-h intervals. Subjects maintained their usual sleep-wake cycles but were awakened for three 30-min periods for night testing. There was no systematic change of baroreflex slope during the 24-h period. There were, however, parallel shifts of the entire sigmoid baroreceptor-cardiac reflex response relation along its R-R interval and arterial pressure axes associated with small, but significant, circadian changes of baseline R-R intervals and arterial pressures. Thus, although our data do not point toward major circadian variability of baro-reflex responsiveness, they provide evidence for an ongoing process of human baroreflex resetting.

Device for rapid quantification of human carotid baroreceptor-cardiac reflex responses.

We designed, constructed, and evaluated a new device to characterize the human carotid baroreceptor-cardiac reflex response relation rapidly. We designed this system for study of reflex responses of astronauts before, during, and after space travel. The system comprises a new tightly sealing silicone rubber neck chamber, a stepping motor-driven electro-deposited nickel bellows pressure system, capable of delivering sequential R-wave-triggered neck chamber pressure changes between +40 and -65 mmHg, and a microprocessor-based electronics system for control of pressure steps and analysis and display of responses. This new system provokes classic sigmoid baroreceptor-cardiac reflex responses with threshold, linear, and saturation ranges in most human volunteers during one held expiration.

Arterial baroreflexes and blood pressure and heart rate variabilities in humans.

The factors responsible for 24-hour blood pressure and heart rate variabilities have never been clarified; however, studies performed in unanesthetized animals have shown an increase in blood pressure variability after sinoaortic denervation, and a negative relationship has been reported occasionally between blood pressure variability and baroreflex control of heart rate in humans. We have systematically investigated this issue in 82 ambulant hypertensive subjects using 24-hour intraarterial blood pressure recording (Oxford method) in which blood pressure and heart rate variabilities were measured by calculating the standard deviations of the values obtained throughout the 24 hours or during separate daytime and nighttime periods. Baroreflex sensitivity was assessed by the bradycardic or tachycardic responses to intravenous injections of phenylephrine or nitroglycerin and by the blood pressure response to changes in carotid transmural pressure obtained with a neck chamber. The sensitivity of the baroreceptor-heart rate reflex as assessed by the vasoactive drug technique showed a negative relationship with 24-hour blood pressure variability as well as with daytime and nighttime blood pressure variabilities measured separately (r = -0.28 to -0.50, p less than 0.05). These variabilities also correlated negatively with the sensitivity of the baroreceptor-blood pressure reflex as assessed by the neck chamber technique. By contrast, baroreflex sensitivity showed a positive correlation with heart rate variabilities (r = 0.32 to 0.47, p less than 0.05). The relationship between baroreflex sensitivity and blood pressure and heart rate variabilities was confirmed when the data were analyzed by multiple regression to adjust for blood pressure and age differences among the 82 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Variability of the haemodynamic responses to laboratory tests employed in assessment of neural cardiovascular regulation in man

In man evaluation of neural cardiovascular regulation makes use of a variety of tests which address the excitatory and reflex inhibitory neural influences that control circulation. Because interpretation of these tests is largely based on the magnitude of the elicited haemodynamic responses, their reproducibility in any given subject is critical. In 39 subjects with continuous blood pressure (intra-arterial catheter) and heart rate monitoring we measured the blood pressure and heart rate rises during hand-grip and cold-pressor test, the heart rate changes occurring during baroreceptor stimulation and deactivation by injection of phenylephrine and trinitroglycerine, and the heart rate and blood pressure changes occurring with alteration in carotid baroreceptor activity by a neck chamber. Each test was carefully standardized and performed at 30 min intervals for a total of six times in each subject. The results showed that the responses to any test were clearly different from one another and that this occurred in all subjects studied. For the group as a whole the average response variability (coefficient of variation) ranged from 10.2% for the blood pressure response to carotid baroreceptor stimulation to 44.2% for the heart rate response to cold-pressor test. The variability of the responses was not related to basal blood pressure or heart rate, nor to the temporal sequence of the test performance. Thus tests employed for studying neural cardiovascular control in man produce responses whose reproducibility is limited. This phenomenon may make it more difficult to define the response magnitude typical of each subject, as well as its comparison in different conditions and diseases.

Carotid baroreflex sensitivity and physical fitness in cycling tourists.

Carotid baroreceptors were stimulated with neck suction in 47 healthy subjects. Pulse interval lengthening was measured and the time course of the response was evaluated. Eight intensities of neck chamber suction were applied to select a criterion for computing the "RR response" that gives a significant linear relationship with the magnitude of the stimuli in the highest number of individuals. The best criterion was the maximal RR prolongation within 5 seconds after the onset of the stimulus. The slope of this relationship was defined as baroreflex sensitivity. The effect of physical fitness on baroreceptor function was investigated in 24 cycling tourists with a wide range of peak oxygen uptake and training characteristics. Baroreflex sensitivity averaged 7.3 +/- 0.8 msec X mm Hg-1 and was not significantly related to age, weight, basal heart rate, peak oxygen uptake and ventilation and other training characteristics. The results suggest that in man the so defined sensitivity of the carotid baroreflex control of heart rate is not influenced by the level of physical fitness and therefore the measurement of these characteristics can be neglected in evaluating baroreflex sensitivity.

Arterial baroreceptor control of blood pressure in man

Information on arterial baroreceptor control of circulation is much more restricted in man than in animals, largely because of the limitations in the techniques available in humans for this type of study. However, recent utilization of the neck chamber technique that addresses the primary function of an arterial baroreflex, i.e. blood pressure control, has provided a significant amount of information. This paper describes baroreceptor control of blood pressure as derived from neck chamber studies in normal people and discusses its modifications by exercise and ageing, and its participation in a phenomenon such as spontaneous blood pressure variability. The description given here is focused on aspects of this baroreceptor control that have changed the concept of the overall arterial baroreceptor function developed by means of techniques for studying only baroreceptor influences on heart rate.

Formula omitted] ratio as an index of autonomic tone changes

The effects of changes in sympathetic tone on QT QS 2 ratio were studied in 10 healthy subjects aged 21 to 24 years. The subjects underwent a bicycle ergometer exercise, a tilt test, a decrease in carotid transmural pressure induced by means of pneumatic neck chamber, an i.v. injection of phenylephrine. A phonocardiogram and ECG were simultaneously recorded at a paper speed of 100 mm/s to evaluate QT and QS 2 intervals in each test. In basal conditions, the QT QS 2 ratio was less than 1, whereas it increased progressively during the physical exercise and became greater than 1 at peak exercise. Both the upright position and the increase in neck-tissue pressure induced a significant increase in the QT QS 2 ratio as compared with the basal values, whereas i.v. administration of phenylephrine reduced significantly the QT QS 2 ratio. These results demonstrate that those stimuli which induce a rise in adrenergic activity may increase the QT QS 2 ratio. In contrast, the reflex inhibition of the adrenergic activity induced by phenylephrine is accompanied by a reduction in QT QS 2 ratio. Therefore, the QT QS 2 ratio might represent a reliable index of sympathetic cardiac tone.

Plasma catecholamines do not invariably reflect sympathetically induced changes in blood pressure in man.

Plasma concentrations of noradrenaline and adrenaline were measured radioenzymatically in nine subjects during 4 min pressor and depressor responses (intra-arterial measurements) induced by increasing and reducing sympathetic vasoconstrictor tone via carotid baroreceptor deactivation and stimulation (neck chamber technique). During the pressor response (15 +/- 3 mmHg, mean +/- SE) plasma noradrenaline and adrenaline showed various changes in the different subjects and on average were not significantly increased above control. During the depressor response (-9 +/- 2 mmHg) plasma noradrenaline and adrenaline also showed various changes in the subjects and were on average not significantly reduced below control. In contrast the same subjects all showed an increase in noradrenaline and adrenaline (average 76 and 117%) at the fourth minute of a tilting manoeuvre with a return to pretilting values no more than 4 min after resumption of the supine position. These results suggest that the moderate and/or restricted alterations in sympathetic tone produced by manipulating a single baroreflex, though capable of affecting blood pressure, are not reflected by alterations in plasma catecholamines. To modify these humoral indices significantly, the more drastic or more diffuse alterations in sympathetic activity that may be produced by manipulating low as well as high pressure reflexogenic areas are needed.

Mechanisms of antihypertensive action of beta-adrenergic blocking drugs: evidence against potentiation of baroreflexes.

A possibility that can be advanced to explain the antihypertensive effect of beta-blocking drugs is that they act through the baroreflex control of the cardiovascular system. In 38 essential hypertensive patients we measured 1) The lengthening and shortening in R-R interval caused by stimulation or deactivation of arterial baroreceptors (vasoactive drug technique); 2) The fall and rise in blood pressure caused by stimulation and deactivation of carotid baroreceptors (neck chamber); 3) The rise in forearm vascular resistance caused by deactivation of cardiopulmonary receptors (lower body suction). The study was made before and after 6-10 days' administration of nadolol (80-360 mg once a day) or acebutolol (200-600 mg t.i.d.). Nadolol and acebutolol similarly reduced blood pressure and heart rate. Either drug increased heart rate responses to arterial baroreceptor manipulation but the increase fell short of statistical significance. Blood pressure and vasomotor responses to carotid baroreceptor and cardiopulmonary receptor manipulation were also not significantly modified by beta blockade. The baroreceptor control of heart rate and blood pressure showed a modification, however, insofar as a resetting towards the lower blood pressure values occurred. These findings demonstrate that arterial baroreceptor and cardiopulmonary receptor control of circulation is not potentiated by beta-blocking drugs, and that therefore this mechanism cannot account for their antihypertensive effect. The resetting of the baroreflex that occurs during beta blockade may, however, contribute to maintain the hypotension obtained.

Modification of arterial baroreflexes by captopril in essential hypertension

Captopril lowers blood pressure without increasing heart rate and plasma norepinephrine, which suggests that this drug may potentiate arterial baroreflexes. In eight subjects with untreated essential hypertension, blood pressure was monitored intraarterially and the effects of baroreceptor stimulation or deactivation were assessed by measuring (1) the slopes of the relations between increase or reduction in systolic pressure (intravenous phenylephrine or nitroglycerin) and the resulting lengthening or shortening in R-R interval, and (2) the increase or decrease in mean arterial pressure induced by increasing and decreasing carotid transmural pressure (neck chamber). The measurements were made before and after a hypotensive oral dose of captopril (50 mg). Before captopril, the slopes of the R-R interval changes with increase and reduction in systolic pressure were 8 and 4 ms/mm Hg, respectively. The slopes of the mean arterial pressure changes with increase and reduction in carotid transmural pressure were 0.51 and 0.40 mm Hg, respectively. After captopril, the responses to baroreceptor stimulation were unaltered but those to baroreceptor deactivation were augmented. The presser and heart rate responses to hand-grip and cold exposure were unchanged by captopril. Administration of captopril is accompanied by a baroreflex potentiation which involves the lower portion of the stimulus-response curve of the reflex. This phenomenon (which may originate at the afferent baroreceptor fibers or centrally) may avoid a reduction in the tonic baroreflex influence during captopril-induced hypotension, thus contributing to the hemodynamic effects of the drug.

Baroreceptor stimulation and isometric exercise in normotensive and borderline hypertensive subjects.

1. The effects of carotid baroreceptor stimulation (neck chamber) on systemic haemodynamics were determined for normotensive and borderline hypertensive subjects during periods of resting and isometric exercise. 2. Both groups reacted to baroreceptor stimulation with a similar decrease in mean arterial pressure and cardiac index at rest and during isometric exercise, but baseline heart rate decreased more in borderline hypertensive patients. 3. Baroreceptor stimulation elicited the same haemodynamic response at rest and during exercise-induced arterial pressure increase. Since the magnitude of arterial pressure had no bearing on the subsequent response, these data suggest resetting of baroreceptors during this short-term blood pressure increase.

Carotid sinus baroreceptor control of arterial pressure in renovascular hypertensive subjects.

We used the neck chamber technique to study carotid baroreceptor control of blood pressure in 18 renovascular hypertensive subjects. Carotid baroreceptors were stimulated or deactivated for 2 minutes by applying graded reductions or increases in the neck tissue pressure (NTP) outside the carotid sinuses. The sensitivity of the baroreflex was separately calculated for these two conditions by the coefficients of the linear regressions relating the changes in NTP to the resulting changes in mean arterial pressure (MAP, catheter measurement). Baroreceptor deactivation increased MAP, and the sensitivity of the baroreflex was 0.12 /+- 0.07 in an early (5 to 1 seconds) and 0.32 /+- 0.05 in a late (90 to 120 seconds) phase of the stimulus application. Baroreceptor stimulation reduced MAP, and the baroreflex sensitivity was in this instance 0.66 /+- 0.08 and 0.05 /+- 0.08 respectively. Both these sensitivities were significantly greater than those obtained for the baroreceptor deactivation. These response entirely reproduced those of essential hypertensive subjects, but differed from those of normotensive subjects in whom baroreflex sensitivity was greater for carotid baroreceptor deactivation than for stimulation. Our findings indicate that carotid baroreceptor control of blood pressure undergoes a marked resetting in renovascular hypertension. The similarity of the baroreflex between renovascular and essential hypertension suggests as secondary origin of the resetting in man.

Baroreflex responsiveness in borderline hypertensives: a study with neostigmine.

The baroreflex response to changes in transmural pressure throughout the arterial tree or limited to the carotid sinus was evaluated in ten borderline hypertensives and compared with that observed in ten normal subjects and in ten established hypertensives. Baroreceptor sensitivity was tested by evaluating both heart rate response to phenylephrine-induced increase in arterial pressure and heart rate and blood pressure changes induced by increased neck tissue pressure by means of a neck chamber. The heart rate response to phenylephrine (evaluated by the regression of the R-R interval versus the systolic blood pressure) was depressed both in borderline and established hypertensives as compared with controls. Similarly, the heart rate and the pressor response to increased neck tissue pressure were depressed in both groups of hypertensives. In borderline, but not in established hypertensives, neostigmine administration improved consistently the pressor baroreflex response to increased neck tissue pressure and the heart rate reflex response to both the employed stimuli. These findings indicate that a reduced parasympathetic activity is one of the components involved in the altered baroreflex sensitivity in borderline hypertensives.

Does the baroreceptor-heart rate reflex indicate the capacity of the arterial baroreceptors to control blood pressure?

1. We have examined the question asked in the title by studying: the carotid baroreceptor reflex in man with a variable-pressure neck chamber; the carotid baroreceptor reflex in conscious rabbits with a variable-pressure capsule around the carotid bifurcation; and the barorecptor-heart rate reflex. 2. At rest, the association between the sensitivities of the carotid baroreceptor-blood pressure and -heart rate reflexes, and of these with the baroreceptor-heart rate reflex, is weak. Exercise causes dissociation between control of blood pressure and heart rate. In hypertension, depression of the baroreceptor-heart rate reflex does not reflect the altered characterisitics of the carotid sinus-blood pressure reflex.

Methyldopa and neural control of circulation in essential hypertension

The effects of methyldopa on hemodynamics at rest and on neural control of circulation were studied in subjects with essential hypertension. Blood pressure (recorded intraarterially), heart rate, cardiac output (thermodilution) and total peripheral resistance were measured before and after 15 to 20 days of continuous administration of the drug (500 to 750 mg twice daily). Methyldopa reduced mean arterial pressure (17 percent) and peripheral resistance (25 percent) without signlficantly affecting heart rate and cardiac output. The various cardiovascular responses to stimuli such as dynamic and isometric exercise and exposure to cold were un-changed by treatment with methyldopa, but the peak blood pressure values during these stimuli were lowered by methyldopa because of reduction of baseline values. Stimulation of carotid sinus baroreflexes (by negative air pressure in a sealed chamber enclosing the neck) also caused the same decrease in arterial pressure, peripheral resistance, heart rate and cardiac output before and during methyldopa treatment; on the other hand, the increase in arterial pressure and peripheral resistance caused by inactivation of baroreflexes (positive air pressure in the neck chamber) was somewhat reduced, although not abolished, by therapy with methyldopa. It is concluded that (1) the hypotensive effect of methyldopa is due to systemic vasodilatation; (2) this drug does not interfere with the cardiovascular responses to various neural excitatory stimuli; and (3) it reduces the ability of the carotid baroreflex to compensate for a decrease in blood pressure. Reduction of this pressor response may explain why methyldopa has a greater antihypertensive effect when patients are standing.