Atrial natriuretic factor (ANF 103-126) enhances volume- and pressor-induced heart rate response in the conscious rat

The reduction in blood pressure due to ANF(103-126) fails to elicit reflex cardioacceleration in the conscious rat. To examine baroreflex sensitivity, the effect of ANF(103-126) on the heart period (HP) response to rapid central volume expansion and to alterations in mean arterial pressure (MAP) induced by bolus injections of phenylephrine and sodium nitroprusside was assessed. ANF(103-126) significantly augmented the bradycardic response induced by acute volume expansion from 426 +/- 21 to 391 +/- 23 beats min-1 versus 421 +/- 23 to 405 +/- 24 without ANF(103-126). Baroreflex sensitivity was defined by the ratio of the change in heart period to the maximal change in mean arterial pressure. The dose of ANF(103-126) utilized did not affect basal heart rate or the magnitude of the mean arterial pressure response to phenylephrine but did significantly enhance the nitroprusside-induced decrease in mean arterial pressure. Baroreceptor sensitivity to phenylephrine was significantly increased by ANF(103-126): 0.997 +/- 0.07 (ms mmHg-1) during ANF(103-126) vs 0.613 +/- 0.08 during vehicle. The total duration of the heart rate response to phenylephrine was also prolonged. In contrast, ANF(103-126) did not alter the baroreceptor sensitivity (1.45 +/- 0.3 vs 1.43 +/- 0.2 ms mmHg-1) or duration of heart rate response to nitroprusside. In the conscious rat, ANF(103-126) modifies the heart rate response to changes in mean arterial pressure and acute central volume expansion. This action appears to be dependent on stimulation of cardiac vagal afferents.     

Atrial natriuretic factor (ANF 103–126) enhances volume- and pressor-induced heart rate response in the conscious rat

The reduction in blood pressure due to ANF(103–126) fails to elicit reflex cardioacceleration in the conscious rat. To examine baroreflex sensitivity, the effect of ANF(103–126) on the heart period (HP) response to rapid central volume expansion and to alterations in mean arterial pressure (MAP) induced by bolus injections of phenylephrine and sodium nitroprusside was assessed. ANF(103–126) significantly augmented the bradycardic response induced by acute volume expansion from 426 ± 21 to 391 ± 23 beats min^-1 versus 421 ± 23 to 405 ± 24 without ANF(103–126). Baroreflex sensitivity was defined by the ratio of the change in heart period to the maximal change in mean arterial pressure. The dose of ANF(103–126) utilized did not affect basal heart rate or the magnitude of the mean arterial pressure response to phenylephrine but did significantly enhance the nitroprusside-induced decrease in mean arterial pressure. Baroreceptor sensitivity to phenylephrine was significantly increased by ANF(103–126): 0.997 ± 0.07 (ms mmHg^-1) during ANF(103–126) vs 0.613 ± 0.08 during vehicle. The total duration of the heart rate response to phenylephrine was also prolonged. In contrast, ANF(103–126) did not alter the baroreceptor sensitivity (1.45 ± 0.3 vs 1.43 ± 0.2 ms mmHg^-1) or duration of heart rate response to nitroprusside. In the conscious rat, ANF(103–126) modifies the heart rate response to changes in mean arterial pressure and acute central volume expansion. This action appears to be dependent on stimulation of cardiac vagal afferents.     

Effect of central venous pressure on arterial baroreflex control of heart rate.

There is considerable evidence that the level of afferent cardiopulmonary receptor activity modulates sinus node responses to arterial baroreflex stimulation in experimental animals. We tested the hypothesis that this reflex interaction occurs also in man by measuring sinus node responses to arterial baroreceptor stimulation with phenylephrine injection or neck suction, before and during changes of central venous pressure provoked by lower body negative pressure or leg and lower trunk elevation. Variations of central venous pressure between 1.1 and 9.0 mmHg did not influence arterial baroreflex mediated bradycardia. Baroreflex sinus node responses were augmented by intravenous propranolol, but the level of responses after propranolol was comparable during the control state, lower body negative pressure, and leg and trunk elevation. Sinus node responses to very brief baroreceptor stimuli applied during the transitions of central venous pressure also were comparable in the three states. We conclude that physiological variations of central venous pressure do not influence sinus node responses to arterial baroreceptor stimulation in man.     

Arterial baroreceptor reflex control of heart rate in two species of turtle

Attempts were made to stimulate an arterial baroreceptor reflex in anesthetized and conscious pond turtles. In turtles anesthetized with either alpha-chloralose or pentobarbital, occlusion of the ascending or descending aortas produced no reflex heart rate (HR) changes. In pentobarbital-anesthetized turtles, direct electrical or mechanical stimulation of potential baroreceptor sites along the central aortic arches and carotid arteries produced no significant changes in either HR or blood pressure (BP). Occlusion of the common carotid arteries also produced no HR or BP changes. Intravenously administered nitroglycerin lowered BP but caused no reflex tachycardia in anesthetized turtles. Phenylephrine and angiotensin elevated BP in the anesthetized turtle but caused no reflex bradycardia. In conscious turtles phenylephrine increased BP and nitroglycerin decreased BP. Neither response produced a statistically significant HR change, although HR tended to decrease transiently with phenylephrine and increase with nitroglycerin. These HR changes were abolished by atropine. Rapid intra-arterial infusion of 6% dextran transiently raised BP but caused no reflex bradycardia. These experiments suggest that cardiovascular regulation in the turtle is accomplished without a major contribution from arterial baroreceptor reflexes.     

Do natriuretic peptides modify arterial baroreflexes in sheep?

While atrial and B-type natriuretic peptides (ANP and BNP) have been shown to enhance reflex responses attributed to cardiac vagal afferents, their effects on arterial baroreceptor reflex function remain controversial. The actions of C-type natriuretic peptide (CNP) in this regard are unknown. To clarify their actions on arterial baroreflexes, we tested whether i.v. infusions of ANP, BNP or CNP at 10 pmol kg(-1) min(-1) modified the steady-state mean arterial blood pressure-heart rate (MAP-HR) relationship in conscious sheep. At this dose, all three natriuretic peptides are known to enhance the cardiac chemoreflex response to phenylbiguanide (Bezold-Jarisch reflex). Sigmoid MAP-HR relationships were constructed from the steady-state responses to alternating injections of vasopressor (phenylephrine, 1-15 microg kg(-1)) and vasodepressor agents (nitroprusside, 1-15 microg kg(-1)) in the absence and presence of infused ANP, BNP or CNP (tested in random order at least 1 week apart). No parameter of the steady-state baroreflex relationship was significantly altered by infusion of any of the three natriuretic peptides. We conclude that in conscious sheep, normal arterial baroreceptor-HR reflex function prevails in the presence of moderate doses of ANP, BNP or CNP.     

Effects of spaceflight on postnatal development of arterial baroreceptor reflex in rats

AIM: It has been reported that spaceflight attenuates the arterial baroreceptor reflex. As this reflex function changes dramatically during postnatal development, we hypothesized that space flight depresses the developmental changes of the reflex system. To test this hypothesis, we evaluated the baroreceptor reflex function in rats, which were exposed to a microgravity environment on a space shuttle 9-25 days after birth. METHODS: Baroreceptor reflex sensitivity and the afferent sensitivity were evaluated by measuring heart rate (HR) and aortic nerve activity (ANA) changes in response to an increase in mean arterial pressure (MBP) derived by phenylephrine injection (20-50 microg kg(-1)) under urethane-anaesthesia. RESULTS: Baroreceptor reflex sensitivity (% change of HR/% change of MBP) was lower in the flight group (FLT: -0.19 +/- 0.04, n = 4) than either the asynchronous ground control group (AGC: -0.47 +/- 0.06, n = 6, P < 0.01) or the vivarium group (VIV: -0.41 +/- 0.07, n = 6, P < 0.05). This was similar to the differences of the afferent sensitivity (% change of ANA/% change of MBP) between FLT (2.07 +/- 0.30) and the control groups (AGC: 2.71 +/- 0.22, n.s.; VIV: 3.00 +/- 0.32, P < 0.05). At the end of 30 days of recovery under normal gravity conditions, however, there were no significant group differences in these parameters. conclusion: These results suggest that the space environment attenuates the postnatal development of the arterial baroreceptor reflex function in rats, which may be partially because of a depression of the postnatal development of the baroreceptor afferents. These functional alterations, however, recover to their normal level on re-exposure to the Earth's gravity.     

Depressed responsiveness of the carotid sinus reflex in conscious newborn animals.

The responsiveness of the carotid sinus reflex was evaluated by comparing the effects of bilateral carotid occlusion (BCO) in conscious adult dogs and puppies on measurements of arterial pressure, cardiac output, heart rate, and calculations of total peripheral resistance (TPR). In eight adult dogs, BCO increased mean arterial pressure by 57 +/- 6%, TPR by 48 +/- 5%, and heart rate by 45 +/- 15%. In puppies, BCO induced smaller increases (P less than 0.05) in mean arterial pressure (30 +/- 5%) and TPR (29 +/- 4%), while heart rate did not change. After elimination of opposing vagal and aortic baroreceptor reflexes, the differences in responses to BCO of mean arterial pressure and TPR between adults and newborns were even greater. Thus, the carotid baroreceptor reflex appears to be depressed in the newborn when compared with the fully developed reflex in the normal, conscious adult.     

Aspects of the Central Integration of Arterial Baroreceptor and Cardiac Ventricular Receptor Reflexes in the Cat

The possible central integrative mechanisms, responsible for the earlier reported, differentiated reflex engagement of the renal and muscle vessels and the heart from cardiac ventricular receptors and arterial baroreceptors, respectively, were analyzed in atropinized cats. The reflex renal vessel, muscle vessel and heart rate responses, expressed as per cent of maximum, to graded activations of arterial baroreceptors (sinus pressure variations) and stimulations of ventricular receptor afferents in the cardiac nerve were systematically compared. Cardiac nerve stimulation with low frequencies was found to elicit more pronounced reflex renal vessel responses than muscle vessel and heart rate responses. In contrast, elevations of sinus pressure induced equally pronounced renal and muscle vessel responses. High frequency cardiac nerve stimulation elicited maximal reflex renal vessel responses, but only submaximal effects on muscle vessels and heart rate, while intense baroreceptor stimulation induced maximal reflex effector responses throughout. The submaximal heart rate response to cardiac nerve stimulation is probably due to a simultaneous activation of excitatory afferents. On the other hand, the less pronounced muscle than renal vessel responses when the cardiac nerve was stimulated probably reflect a relatively sparse innervation of muscle vasomotor neurons by ventricular receptor afferents, which seem instead to be preferentially oriented towards renal vasomotor and, possibly, cardiac motor neurons.     

Aspects of the central integration of arterial baroreceptor and cardiac ventricular receptor reflexes in the cat.

The possible central integrative mechanisms, responsible for the earlier reported, differentiated reflex engagement of the renal and muscle vessels and the heart from cardiac ventricular receptors and arterial baroreceptors, respectively, were analyzed in atropinized cats. The reflux renal vessel, muscle vessel and heart rate responses, expressed as per cent of maximum, to graded activations of arterial baroreceptors (sinus pressure variations) and stimulations of ventricular receptor afferents in the cardiac nerve were systematically compared. Cardiac nerve stimulation with low frequencies was found to elicit more pronounced reflex renal vessel responses than muscle vessel and heart rate responses. In contrast, elevations of sinus pressure induced equally pronounced renal and muscle vessel responses. High frequency cardiac nerve stimulation elicited maximal reflex renal vessel responses, but only submaximal effects on muscle vessels and heart rate, while intense baroreceptor stimulation induced maximal reflex effector responses throughout. The submaximal heart rate response to cardiac nerve stimulation is probably due to a simultaneous activation of excitatory afferents. On the other hand, the less pronounced muscle than renal vessel responses when the cardiac nerve was stimulated probably reflect a relatively sparse innervation of muscle vasomotor neurons by ventricular receptor afferents, which seem instead to be preferentially oriented towards renal vasomotor and, possibly, cardiac motor neurons.     

Baroreflex “resetting” by arterial hypoxia in the renal and cardiac sympathetic nerves of the rabbit

1. Renal and cardiac sympathetic baroreflex functions were studied in sodium pentobarbitone anaesthetized rabbits given succinylcholine, during constant artificial ventilation with air and with hypoxic gas mixtures. Mean arterial pressure (MAP) was raised and lowered between values of 40 and 140 mm Hg by means of aortic and vena caval periovascular balloons and integrated sympathetic nerve activity (SNA) was recordered. 2. The relationship between MAP and SNA was sigmoid, with upper and lower plateau levels. The curves were defined by calculating median blood pressure, SNA Range and reflex gain. In both renal and cardiac sympathetics section of the carotid sinus and aortic nerves completely abolished the MAP-related changes in SNA. 3. The renal baroreflex curves were reset from control levels during hypoxia. Median blood pressure increased, as did SNA Range and gain. These effects were due to central interactions between arterial baroreceptor, arterial chemoreceptor and vagal afferent activity. 4. The cardiac sympathetic baroreflex curves were shifted in the opposite direction from control with reduction in median blood pressure, SNA Range and reflex gain. These changes were due to chemoreceptor-arterial baroreceptor interactions. 5. Arterial hypoxia thus evokes a differentiated pattern of baroreflex resetting in the renal and cardiac sympathetic montoneuron pools with differing changes in neural response range and sensitivity to arterial pressure changes.     

Cardiac vagal and sympathetic nerve responses to baroreceptor stimulation in the dog

The effects of ascending stepwise pressure changes in the isolated carotid sinuses on cardiac vagal and sympathetic nerve activities were studied in anesthetized, open chest dogs. The steady state responses of the cardiac vagal and the sympathetic nerve activity and arterial blood pressure were plotted against the sinus pressure and the relations were approximated by the normal distribution function (response curve). The sinus pressure- vs. reflex gain relations (reflex gain curve) were approximated by the normal density function. The maximum gain and the range of change were found to be greater for the vagal than for the sympathetic and arterial pressure responses. The sinus pressure values derived from response curves and reflex gain curves for vagal and sympathetic nerve responses were close to each other, while these values and those obtained from arterial pressure responses were considerably apart. It was concluded that: (1) The cardiac vagal neurons are more sensitive to the baroreceptor input than the sympathetic neurons; (2) The similar type of baroreceptor afferent inputs reach the cardiac vagal and the sympathetic structures which are controlling the autonomic outflows.     

Effect of carotid sinus nerve stimulation pattern on cardiorespiratory responses.

The reflex responses to steady and intermittent stimulation of the carotid sinus nerve (CSN) were compared in anesthetized dogs. Intermittent stimulation was less effective than steady stimulation in reducing the arterial blood pressure, and the disparity was exaggerated after acute sinoaortic denervation. With the sinoaortic nerves intact, at low mean stimulation frequencies the heart rate responses were greater during intermittent than during steady CSN stimulation. At higher mean stimulation frequencies, however, steady CSN stimuli were more effective than were the intermittent type. After sinoaortic denervation, steady stimuli evoked greater heart rate responses than did intermittent stimuli over the entire mean frequency range studied. Reflex changes in respiratory depth and frequency were also greater during steady than during intermittent CSN stimulation. The greater efficacy of steady than of intermittent stimulation in evoking.the observed reflex cardiovascular and respiratory changes is probably ascribable to the pronounced frequency limitation at the first synapse of the baroreceptor reflex in the brain.     

Circulatory effects of carotid sinus stimulation and changes in blood volume distribution in hypertensive man

In 8 patients with moderate hypertension and 8 normotensive subjects an attempt was made to study the circulatory effects of high and low pressure baroreceptor stimulation. Intrathoracic low pressure receptors were stimulated by changes in blood volume distribution using lower body negative pressure (LBNP) and lower body positive pressure (LBPP). The carotid sinus was stimulated by sinusoidal neck suction. Blood pressure, central venous pressure, heart rate, cardiac output and forearm blood flow were recorded. During LBNP and LBPP changes in central blood volume, reflected in changes in central venous pressure, induced significantly greater changes in cardiac output and forearm blood flow in the hypertensive subjects. In both normotensive and hypertensive subjects mean arterial blood pressure was essentially unchanged during LBNP and a slight increase was found during LBPP. Heart rate and blood pressure response to stimulation of the carotid sinus decreased with increasing resting mean arterial pressure. The results suggest impairment of reflex adjustments, via arterial baroreceptors, possibly in particular to dynamic stimuli, rather than via intrathoracic “low pressure” baroreceptors in subjects with moderate hypertension.     

Modulation of the human nociceptive flexion reflex across the cardiac cycle

Carotid baroreceptor stimulation has been shown to dampen pain. This study tested, in 40 normotensive adults, the hypothesis that pain is lower during systole when arterial baroreceptor stimulation is maximal than diastole when stimulation is minimal. The sural nerve was stimulated electrocutaneously to obtain a nociceptive flexion reflex (NFR) threshold, and then stimulation was delivered for 28 trials at 100% NFR threshold at seven intervals after the R-wave. Nociceptive responding was indexed by electromyographic (EMG) activity elicited in the biceps femoris. Significant variations in EMG activity occurred across the cardiac cycle, with less activity midcycle, indicating that the NFR response was attenuated during systole compared to diastole. Stimulation of baroreceptors by natural changes in blood pressure during the cardiac cycle dampened nociception, and accordingly, the data support the arterial baroreflex mechanism of hypertensive hypoalgesia.     

The cause of the difference between the arterial baroreceptor reflex under natural pulsatile circulation and under nonpulsatile systemic circulation

In a previous study we investigated the relation between afferent and efferent activity of the arterial baroreceptor reflex under nonpulsatile systemic circulation using total left heart bypass. The results indicated that the regulation of the arterial baroreceptor reflex was converted under nonpulsatile systemic circulation, and we inferred that a possible reason for this conversion was the transformation in discharge of the afferent activity of the arterial baroreceptor reflex that took place under nonpulsatile systemic circulation. In the present study we tested this hypothesis by sectioning carotid sinus and aortic depressor nerves and electrically stimulating bilateral aortic depressor nerves under anesthesia in five rabbits (400 spikes for 20s, with 0.02ms pulse width and 8 V amplitude), while recording changes in aortic pressure, mean aortic pressure, and heart rate. Continuous stimulation was taken as discharge of the afferent activity of the arterial baroreceptor reflex under nonpulsatile systemic circulation, and periodic stimulation was taken as discharge under natural pulsatile circulation. Aortic pressure, mean aortic pressure, and heart rate decreased under both continous and periodic stimulation. The decreases in mean aortic pressure and heart rate during continuous stimulation were significantly lower than those during periodic stimulation. Our results suggest that the transformation in discharge of the afferent activity of the arterial baroreceptor reflex under nonpulsatile systemic circulation may have played an important causative role in the conversion of the regulation of the arterial baroreceptor reflex under nonpulsatile systemic circulation.     

Functional changes in autonomic nervous system and baroreceptor reflex induced by 14 days of 6° head-down bed rest

We studied the effects of 14 days of 6° head-down bed rest (HDBR) in 16 healthy male subjects to examine the functional changes in the autonomic nervous system and cardiac baroreceptor reflex response with an emphasis on dynamic changes during HDBR. Beat-by-beat RR intervals (RRIs) and systolic arterial pressures (SAPs) were measured non-invasively from simultaneous, continuous recordings of ECG and arterial pressure waves in supine resting postures. A power spectrum analysis by the fast Fourier transform was applied to a data set composed of interpolated 512 RRIs and 512 SAPs (256 s in duration). Three indices of cardiac baroreceptor reflex sensitivity (BRS) were obtained by applying a sequence technique and a cross-spectrum analysis technique to the spontaneous RRIs and SAPs. The high-frequency band power of RRI variability (HF_RRI) decreased significantly in the latter part of HDBR and persisted until the initial stage of the post-HDBR period (POST). The low-frequency band power of SAP variability decreased significantly only during the mid-part of HDBR. The BRS_sequence obtained by the sequence technique showed a significant increase temporarily on the initial day of HDBR. The BRS_sequence and the estimate of BRS obtained by the cross-spectrum analysis handling the high-frequency band were both significantly decreased on the initial day of POST. Each of the BRS estimates correlated negatively with heart rate and positively with HF_RRI during HDBR and POST. These results suggest the following: (1) cardiac spontaneous baroreceptor reflex sensitivity might be transiently increased at the initial stage of HDBR, (2) the reduction in vagal modulation on the sinus node occurs from the latter part of HDBR to the initial stage of POST, (3) sympathetic vasomotor control is probably slightly inhibited during the mid-part of HDBR, and (4) the enhancement in cardiac sympathetic modulation and the impairment in cardiac spontaneous baroreceptor reflex sensitivity may occur in the initial stage of POST.     

Studies on the central integration of excitatory chemoreceptor influences and inhibitory baroreceptor and cardiac receptor influences.

Experiments were performed on cats to explore the integrated cardiovascular responses when excitatory (chemoreceptor) and inhibitory (baroreceptor or cardiac receptor) influences are simultaneously presented to the medullary cardiovascular areas. At a given sinus pressure in the low or medium pressure range, the systemic blood pressure and the vascular resistance were higher when the chemoreceptors were stimulated, while a high, pulsating sinus pressure, i.e.a strong baroreceptor stimulation, could suppress completely even an intense chemoreceptor activation. Thus, the set point and the gain of the baroreflex were increased by a concomitant chemoreceptor activation. These effects are compatible with a simple, mutual 'summation' of excitatory and inhibitory influences on a common population of central vasomotor neurons. The reflex vasodilator effects elicited via vagal cardiac afferents were found to be more effectively suppressed by a concomitant chemoreceptor stimulation than were the baroreceptor effects, provided a primary chemoreceptor response (bradycardia) was at hand, while the heart rate responses were essentially uninfluenced by the prevailing chemoreceptor activity. This chemoreceptor suppression of the reflex vasodilatation from cardiac receptors, which may be of great importance in hypoxic situations, e.g. during a dive, suggests a more complex, neuronal interaction between the two reflex mechanisms in the CNS.     

Nutrient control of cardiac rate in the infant rat: alpha-adrenergic mechanisms

Changes in level of nutrient intake have been shown to exert a major influence on beta-adrenergic cardiac activity in 2 week old suckling rats. A series of experiments demonstrates that the alpha-adrenergic vasoconstrictor system is functional by 2 weeks postnatal age, and that alpha-adrenergic blockade with phenoxybenzomine (PBZ) does not affect the high heart rates of well-fed pups but prevents development of the bradycardia after cessation of suckling and fully reverses the low heart rates of nutrient-deprived pups in a dose-dependent manner. This last effect is dependent upon beta-adrenergic reflex cardiac pathways. After PBZ, milk feeding no longer produces cardiac acceleration in nutrient-deprived pups. Systolic and mean arterial pressure during PBZ administration and estimates of plasma volume change during nutrient deprivation are consistent with the inference that changes in peripheral resistance, mediated by the alpha-adrenergic vasoconstrictor system, accompany nutrient regulation of cardiac rate in the suckling rat.     

Convergence of noxious and non-noxious cutaneous afferents and baroreceptor afferents onto single adrenal sympathetic neurons in anesthetized rats

Single units of the adrenal sympathetic nerve (n = 46) were dissected and characterized with respect to tonic discharge and response to cutaneous and baroreceptor stimulation. The frequency of tonic discharge averaged 1.6 Hz and cardiovascular rhythmic modulation was observed in 53% of the units. The stimuli employed in the present study included phenylephrine-induced increases in blood pressure and pinching or brushing of lower chest skin. Mean unit activity increased 27% on lower chest pinching stimulation, decreased 12% on lower chest brushing stimulation and decreased 62% on phenylephrine-induced baroreceptor stimulation. Although there was a tendency for units with higher tonic firing frequency to have a greater response to stimulation, this relationship was not significant for pinching or brushing of lower chest skin. The close correlation between tonic activity and response to phenylephrine was explicable on the basis of a near total depression of many units, which resulted in a larger decrease in firing frequency for units with initially high spontaneous discharge rates. As might be expected, units with cardiovascular rhythmicity manifested greater responses to baroreceptor activation. This correlation was independent of tonic rate of discharge since rhythmic and non-rhythmic units did not significantly differ in tonic activity. While a majority of units responded in a typical fashion to all three stimuli (i.e. with increases to pinching and decreases to brushing and phenylephrine administration), there was little correlation between the response magnitude of individual units to any two of the stimuli employed. We conclude, therefore, that most adrenal sympathetic units receive convergent reflex input from cutaneous noxious and non-noxious afferents as well as from baroreceptor afferents, although for any individual unit the quantitative significance of each input varies.