Characteristics of brachiocephalic and carotid sinus baroreceptors with non-medullated afferents in rabbit

The characteristics of brachiocephalic and carotid sinus baroreceptors with non-medullated afferents have been studied in rabbits. The conduction velocities of 18 non-medullated fibers arising from the brachiocephalic baroreceptors were 0.4-0.8 m/s (0.59 +/- 0.03 m/s, mean +/- SE) and their thresholds were 74-104 mmHg (84 +/- 2 mmHg). 29 non-medullated carotid sinus baroreceptor afferents had thresholds ranging from 60 to 125 mmHg (92 +/- 3 mmHg). Their conduction velocities were 0.5-1.1 m/s (0.65 +/- 0.05 m/s). Blood pressure-baroreceptor response curves of both the brachiocephalic and the carotid sinus baroreceptors were constructed. As the aortic arch non-medullated baroreceptor afferents, the brachiocephalic and the carotid sinus baroreceptors with non-medullated afferents exhibited thresholds about 30 mmHg higher than the medullated ones, considerably lower firing rates, comparatively rapid adaptation and remarkable irregular discharge pattern. It is suggested that the non-medullated baroreceptor afferents are of little importance for the cardiovascular regulation under normal conditions but are likely to play an important role during a sudden rise in arterial pressure.     

Interaction between the baroreceptor and Bezold-Jarisch reflexes

The interaction between the carotid baroreflex and Bezold-Jarisch (BJ) reflex (intravenously administered veratridine) was studied in anesthetized rabbits after aortic nerve section. The carotid sinuses were vascularly isolated to regulate the intrasinus pressure (ISP). The extent of BJ reflex bradycardia and hypotension was progressively diminished as the ISP was elevated stepwise. When the carotid baroreflex was not operative by holding the ISP constant at control, the BJ reflex changes in heart rate (HR) and systemic arterial pressure (SAP) were not significantly different from those induced at the normal condition. Thus the calculated baroreflex static loop gain was greatly decreased during the BJ reflex. However, sinus denervation, analogous to keeping ISP below 50 mmHg, significantly enhanced the BJ reflex effects. A steady-state infusion of veratridine remarkably reduced the slope of the baroreflex function ISP-SAP and ISP-HR curves. The results indicate that the BJ reflex effects are affected by the prevailing arterial baroreceptor input, varying inversely with the ISP level. An attenuation in the baroreflex sinsitivity, in terms of the loop gain or slope of the transfer function curve, was observed during the BJ reflex. The presence of tonic cardiovascular inhibitions exerted by the arterial baroreceptors tends to reduce the BJ reflex bradycardia and hypotension, but the baroreceptors do not function adequately in buffering the cardiovascular inhibition produced by the cardiogenic reflex.     

Baroreflex and somato-reflex control of blood pressure, heart rate and renal sympathetic nerve activity in the obese Zucker rat

It has been reported that the baroreflex control of heart rate (HR) and sympathetic nerve activity (SNA) is attenuated in obese Zucker rats (OZRs) compared with age-matched lean animals (LZRs). What is not known, however, is the extent to which the baroreflex control of mean arterial blood pressure (MAP) is altered in the OZR. In addition, it is not known whether the interactions of other sensory nerve inputs on autonomic control are altered in the OZR compared with the LZR. The aim of this study was to determine the baroreflex control of MAP, HR and renal SNA (RSNA) in the OZR and LZR using an open-loop baroreflex approach. In addition, the effect of brachial nerve stimulation (BNS) on the baroreflex control was determined in these animals. Age-matched, male LZRs and OZRs were anaesthetized, and the carotid baroreceptors were vascularly isolated, bilaterally. The carotid sinus pressure was increased in 20 mmHg increments from 60 to 180 mmHg using an oscillating pressure stimulus. Baroreflex function curves were constructed using a four-parameter logistic equation, and gain was calculated from the first derivative, which gave a measure of baroreceptor sensitivity, before and during BNS. The range over which the baroreflex could change MAP (28 ± 6 versus 87 ± 5 mmHg; mean ± SEM), HR (17 ± 4 versus 62 ± 11 beats min(-1)) and normalized RSNA (NormNA; 22 ± 4 versus 76 ± 11%) was significantly decreased in the OZR compared with the LZR. Likewise, the maximal gain was lower in the OZR, as follows: MAP -0.88 ± 0.22 versus -2.26 ± 0.17; HR -0.42 ± 0.18 versus -1.44 ± 0.22 beats min(-1); and NormNA -0.54 ± 0.14 versus -1.65 ± 0.30% mmHg(-1). There was no difference in the mid-point of the baroreflex curve for each variable between the OZR and LZR. However, the minimal values obtained when the baroreceptors were maximally loaded were higher in the OZR (MAP 68 ± 5 versus 53 ± 4 mmHg; HR 455 ± 7 versus 390 ± 13 beats min(-1); and NormNA -19 ± 4 versus -48 ± 8%). Brachial nerve stimulation in the LZR resulted in an upward and rightward resetting of the baroreflex control of MAP and RSNA, and abolished baroreflex control of HR. The baroreflex control of RSNA in the OZR during BNS was further attenuated and reset upwards and to the right, while the HR response was abolished. With respect to MAP, the baroreflex curve reset upwards and to the right to a point comparable with the LZR during BNS. These data show that there is an attenuated baroreflex control in the OZR and that the ability to reset to higher arterial pressure during somatic afferent nerve stimulation is similar to that in the LZR.     

Carotid-cardiac baroreflex function does not influence blood pressure regulation during head-up tilt in humans

The influence of the carotid-cardiac baroreflex on blood pressure regulation was evaluated during supine rest and 40 degrees head-up tilt (HUT) in 9 healthy young subjects with and without full cardiac vagal blockade. The carotid baroreflex responsiveness, or maximal gain (G(MAX)), was assessed from the beat-to-beat changes in heart rate (HR) and mean arterial pressure (MAP) by the variable neck pressure and suction technique ranging in pressure from +40 to -80 Torr, with and without glycopyrrolate (12.0 +/- 1.0 microg/kg body weight; mean +/- SE). In the supine position, glycopyrrolate increased the HR to 91 +/- 3 bpm, from 54 +/- 3; MAP to 89 +/- 2 mmHg, from 76 +/- 2; and cardiac output to 6.8 +/- 0.3 l.min(-1), from 4.9 +/- 0.3 (P < 0.05). The G(MAX) of the carotid baroreflex control of HR was reduced to -0.06 +/- 0.01 bpm.mmHg(-1), from -0.30 +/- 0.02 (P < 0.05) with no significant effect on the G(MAX) of the carotid baroreflex control of MAP. During HUT the carotid baroreflex control of MAP was unchanged, though the G(MAX) of the carotid baroreflex control of HR was increased (P < 0.05). During HUT, central blood volume, assessed by electrical thoracic admittance, and total vascular conductance were decreased with and without glycopyrrolate. Furthermore, glycopyrrolate reduced G(MAX) of the carotid baroreflex control of HR during HUT (P < 0.05) with no significant effect on G(MAX) of the carotid baroreflex control of MAP. These data suggest that during supine rest and HUT-induced decreases in central blood volume, the carotid baroreflex control of HR is mediated primarily via parasympathetic activity. Furthermore, the maintenance of arterial blood pressure during postural stress is primarily mediated by arterial and cardiopulmonary reflex regulation of sympathetic activity and its effects on the systemic vasculature.     

Discharges of aortic and carotid sinus baroreceptors during spontaneous motor activity and pharmacologically evoked pressor interventions

Our laboratory has demonstrated that the cardiomotor component of aortic baroreflex is temporarily inhibited at the onset of spontaneous motor activity in decerebrate cats, without altering carotid sinus baroreflex. A reason for this dissociation may be attributed to a difference in the responses between aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity. The stimulus–response curves of AoNA and CsNA against mean arterial blood pressure (MAP) were compared between the pressor interventions evoked by spontaneous motor activity and by intravenous administration of phenylephrine or norepinephrine, in which the responses in heart rate (HR) were opposite (i.e., tachycardia vs. baroreflex bradycardia), despite the identical increase in MAP of 34–40 mmHg. In parallel to the pressor response, mean AoNA and CsNA increased similarly by 78–81 and by 88 % of the baseline control, respectively, irrespective of whether the pressor response was evoked by spontaneous motor activity or by a pharmacological intervention. The slope of the stimulus–response curve of the mean AoNA became greater (P < 0.05) during spontaneous motor activity as compared to the pharmacological intervention. On the other hand, the stimulus–response curve of the mean CsNA and its slope were equal (P > 0.05) between the two pressor interventions. Furthermore, the slopes of the stimulus–response curves of both diastolic AoNA and CsNA (defined as the minimal value within a beat) exhibited a greater increase during spontaneous motor activity. All differences in the slopes of the stimulus–response curves were abolished by restraining HR at the intrinsic cardiac frequency. In conclusion, mean mass activities of both aortic and carotid sinus baroreceptors are able to encode the beat-by-beat changes in MAP not only at rest but also during spontaneous motor activity and spontaneous motor activity-related reduction of aortic baroreceptor activity is denied accordingly.     

The polycationic compound gentamicin inhibits the calcium paradox in guinea-pig hearts.

The polycationic drug gentamicin and two calcium antagonists were studied with respect to their protecting action against the calcium paradox in perfused guinea-pig hearts. Besides the mechanograms the release of creatine kinase was recorded; in parallel experiments the Na(+)-content of the hearts was measured before and at the end of the Ca(2+)-lack period, and during re-exposure to normal [Ca2+]0. The calcium paradox was induced by perfusion, for 50 s, with Ca(2+)-free solution containing EGTA (3 x 10(-4) M). Nifedipine and verapamil in concentrations which reduced the equilibrium contractile force by 50%, only mitigated the extent of the calcium paradox, whereas gentamicin applied in a concentration also reducing the contractile amplitude by 50% was able to suppress the calcium paradox completely. The dose-response curves for nifedipine, with respect to the reduction of contractile force and contracture, were identical. In contrast, gentamicin was more effective in attenuating the contracture of the paradox than in reducing the equilibrium contractile force. The large gain of Na+ during the Ca(2+)-lack period was diminished by both nifedipine and gentamicin. The partial protection of calcium antagonists can be related to their interference with the uptake of Na+ through L-type Ca(2+)-channels during the Ca(2+)-lack period, whereas gentamicin seems to act by an additional inhibition of the Na/Ca exchange during the re-exposure to normal [Ca2+]0.     

The influence of heart rate on baroreceptor fibre activity in the carotid sinus and aortic depressor nerves of the rabbit

The arterial baroreceptors and their afferent fibres provide the sensory arm of the reflex that regulates systemic arterial pressure. We have examined whether the relationship between mean baroreceptor discharge and mean arterial pressure is altered when heart rate changes. Experiments were performed on pentobarbitone-anaesthetized rabbits. We recorded the activity of single and multifibre preparations of the carotid sinus (CSN) and aortic depressor nerves (ADN). Data were collected under control conditions and while heart rate was increased by approximately 30-35% by right atrial pacing. Baroreceptor regions were exposed to ramps of pressure (from approximately 25 to 140 mmHg, at approximately 0.5-1 mmHg s(-1)), generated by inflation and deflation of cuffs placed around the inferior vena cava and descending thoracic aorta. Response curves relating baroreceptor discharge to mean pressure were constructed and fitted with third-order polynomial expressions. To provide a measure of an effect of an increase in heart rate on the response curve in the region of the normal operating pressure, we calculated the position of the test response curve relative to the position of the control curve at 90 mmHg (deltaBP(90)). For the ADN, the activity of single fibres (presumptive myelinated fibres) was unaffected by increasing heart rate (deltaBP(90) = +0.1 +/- 1.0 mmHg), while single fibres in the CSN showed a small increase in activity (deltaBP(90) = -1.5 +/- 0.3 mmHg). In multifibre preparations there was a small increase in activity that may be attributable to additional activity in unmyelinated fibres (ADN, deltaBP(90) = -3.4 +/- 1.2 mmHg; CSN, deltaBP(90) = -5.2 +/- 0.9 mmHg). We conclude that the mean discharge of arterial baroreceptors remains a reliable index of mean arterial pressure in the presence of substantial changes in heart rate.     

Carotid baroreflex regulation of vascular resistance in high-altitude Andean natives with and without chronic mountain sickness

We investigated carotid baroreflex control of vascular resistance in two groups of high-altitude natives: healthy subjects (HA) and a group with chronic mountain sickness (CMS), a maladaptation condition characterized by high haematocrit values and symptoms attributable to chronic hypoxia. Eleven HA controls and 11 CMS patients underwent baroreflex testing, using the neck collar method in which the pressure distending the carotid baroreceptors was changed by applying pressures of -40 to +60 mmHg to the chamber. Responses of forearm vascular resistance were assessed from changes in the quotient of blood pressure divided by brachial artery blood velocity. Stimulus-response curves were defined at high altitude (4338 m) and within 1 day of descent to sea level. We applied a sigmoid function or third-order polynomial to the curves and determined the maximal slope (equivalent to peak gain) and the corresponding carotid pressure (equivalent to 'set point'). The results showed that the peak gains of the reflex were similar in both groups and at both locations. The 'set point' of the reflex, however, was significantly higher in the CMS patients compared to HA controls, indicating that the reflex operates over higher pressures in the patients (94.4 +/- 3.0 versus 79.6 +/- 4.1 mmHg; P < 0.01). This, however, was seen only when subjects were studied at altitude; after descent to sea level the curve reset to a lower pressure with no significant difference between HA and CMS subjects. These results indicate that carotid baroreceptor control of vascular resistance may be abnormal in CMS patients but that descent to sea level rapidly normalizes it. We speculate that this may be explained by CMS patients having greater vasoconstrictor activity at altitude owing to greater hypoxic stimulation of chemoreceptors.     

Interaction between "mental stress" and baroreceptor reflexes concerning effects on heart rate, mean arterial pressure and renal sympathetic activity in conscious spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were compared concerning the interactions between cortico-hypothalamic alerting responses and baroreflex influences on neurogenic cardiovascular control. For this purpose mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were continuously recorded during night time in conscious, otherwise undisturbed rats. Baroreceptor sensitivity was assessed as percentage HR and RSNA reductions per mmHg MAP elevation when a standardized phenylephrine infusion was performed. A state of acute "mental stress" could be induced by a likewise standardized sudden blowing of air. These two opposing influences on neurogenic cardiovascular control were also experimentally superimposed in various ways and the effects on MAP, HR and RSNA followed. During "rest" RSNA was higher in SHR than in WKY and it also increased more during "mental stress". The baroreflex sensitivity was clearly reduced in SHR and WKY concerning HR reduction (0.44 +/- 0.06 vs. 0.78 +/- 0.08%/mmHg; p less than 0.01) but not so concerning RSNA, which was similar in SHR and WKY (2.6 +/- 0.2 vs. 2.9 +/- 0.4%/mmHg). If expressed (HR + 1 +/- 3%; p less than 0.025 vs. SHR and RSNA + 11% +/- 10, p less than 0.01 vs. SHR). These results) (0.10 +/- 0.02 vs. 0.06 +/- 0.01 microV/mmHg; p less than 0.12). Also single fibre recordings in anaesthetized rats showed the same principle difference between SHR and WKY.(ABSTRACT TRUNCATED AT 250 WORDS)     

Baroreflex inhibition of the human sinus node: importance of stimulus intensity, duration, and rate of pressure change.

1. Carotid baroreceptors were stimulated with electronically controlled neck suction in five healthy young men and pulse interval prolongation was measured. Timing of the onset of stimuli in relation to cardiac activity was held constant, and stimulus intensity, duration, and dP/dt were varied independently. 2. In the subjects studied, sinus node responses to neck suction were proportional to dP/dt. However, variations of stimulus dP/dt within or above the normal range for arterial dP/dt did not influence the magnitude of integrated baroreflex responses, or the earliest portion of baroreflex sinus node inhibition. 3. Carotid baroreflex responses were linear over a wide range which extended beyond the normal range for human systolic arterial pressures. 4. Saturation of the carotid baroreceptor-cardiac reflex occurred at distending pressures of about 160 mmHg. 5. The average baroreflex responses of the group studied were highly reproducible over time. 6. Baroreflex gain correlated very strongly with base line pulse interval. 7. The magnitude of baroreflex responses increased linearly with the duration of carotid sinus distension and reached a maximum level with stimuli lasting 0-5 sec or more. 8. The results demonstrate that carotid sinus transfer characteristics can be measured in normal man, and that human response patterns are strikingly similar to those observed earlier in experimental animals.     

Role of Ca2+ in genesis of lower esophageal sphincter tone and other active contractions.

The effects of absent or low Ca2+ (0.5 mM), verapamil, nifedipine, Na nitroprusside, theophylline, La2+, and ethanol on basal active tension (tone), "off" contractions, and carbachol contractions were studied in opossum lower esophageal sphincter strips. Incubation in Ca2+-free Ringer (0.1 mM EGTA) abolished tone and contractions. Low Ca2+, verapamil, nifedipine, and theophylline depressed tone more rapidly than "off" contractions. Only verapamil and nifedipine depressed carbachol contractions. Na nitroprusside rapidly depressed tone but left contractions unchanged. La3+ at 1 X 10(-3) M behaved like Ca2+-free incubation but produced sustained contractions with muscle stimulation. Ethanol depressed "off" contractions more than tone and did not affect carbachol-induced contractions. These results suggest that tone probably results from inward leak of Ca2+, whereas "off" contractions depend on release of Ca2+ sequestered in the cell by a mechanism not immediately dependent on increased Ca2+ influx. Carbachol may increase Ca2+ influx as well as utilize sequestered Ca2+. Nifedipine and verapamil may act to block both resting and stimulated Ca2+ influx. Na nitroprusside may act by increasing Ca2+ efflux. Ethanol may act by decreasing the availability of sequestered Ca2+ or by inhibiting the function of a mediator responsible for "off" contractions.     

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.     

Intravenous angiotensin II does not affect dynamic baroreflex characteristics of the neural or peripheral arc

Although the elevation of angiotensin II (Ang II) associated with cardiovascular diseases has been considered to suppress the arterial baroreflex function, how Ang II affects dynamic arterial pressure (AP) regulation remains unknown. The aim of the present study was to elucidate the acute effects of Ang II on dynamic AP regulation by the arterial baroreflex. In seven anesthetized Japanese white rabbits, we randomly perturbed intra-carotid sinus pressure (CSP) according to a binary white noise sequence while recording renal sympathetic nerve activity (RSNA) and AP. We estimated the neural arc transfer function from CSP to RSNA and the peripheral arc transfer function from RSNA to AP before and after 30-min intravenous administration of Ang II (100 ng/kg/min). Ang II increased mean AP from 75.7 +/- 3.1 to 95.5 +/- 5.1 mmHg (p < 0.01), while it did not affect mean RSNA (from 5.9 +/- 1.3 to 5.7 +/- 1.2 a.u.). The neural arc transfer functions did not differ before or after Ang II administration (dynamic gain: -0.94 +/- 0.04 vs. -0.94 +/- 0.13, corner frequency: 0.06 +/- 0.01 vs.0.06 +/- 0.01 Hz, pure delay: 0.16 +/- 0.01 vs. 0.17 +/- 0.02 s). The peripheral arc transfer function did not differ before or after Ang II administration (dynamic gain: 1.18 +/- 0.05 vs. 1.06 +/- 0.11, natural frequency: 0.07 +/- 0.01 vs. 0.08 +/- 0.01 Hz, damping ratio: 1.19 +/- 0.06 vs. 1.24 +/- 0.19, pure delay: 0.83 +/- 0.06 vs. 0.78 +/- 0.05 s). Intravenous Ang II hardly affects the dynamic characteristics of neural and peripheral arc around the physiological operating pressure.     

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.     

A comparison of the stimulus-response curves of aortic and carotid sinus baroreceptors in decerebrated cats

Recordings of total nerve activity suggested differences in the sensitivities and working ranges between aortic and carotid sinus baroreceptors. This result however, conflicts with single fibre studies from isolated receptor zones. Thus it appeared of some interest to compare the function curves of aortic and carotid sinus baroreceptors in the intact animal.This was achieved by comparing the response characteristics of two groups of aortic and carotid sinus baroreceptors in decerebrated cats. One smaller group consisted of 11 receptor pairs, each member of the pair being studied simultaneneously in the same cat, and a larger group consisting of 98 aortic and 49 carotid sinus baroreceptors studied independently of each other.The response of each receptor to wide pressure variations was recorded by inflating and deflating an intraaortic catheter tip balloon. Function curves were derived by plotting receptor discharge in terms of spikes per second against mean aortic pressure. No significant differences were found either in the slope of the function curves or their mean pressures at minimum activity, the latter appearing to be set by the working blood pressure level.Thus it was concluded that aortic and carotid sinus baroreceptors differ neither in their sensitivities nor in their working ranges when in their physiological environment.The support of the Deutsche Forschungsgemeinschaft through the Sonderforschungsbereich 30, Kardiologie Düsseldorf is gratefully acknowledged     

Bezold-Jarisch reflex blunts arterial baroreflex via the shift of neural arc toward lower sympathetic nerve activity

Although the Bezold-Jarisch (BJ) reflex is potentially evoked during acute myocardial ischemia or infarction, its effects on the static characteristics of the arterial baroreflex remain to be analyzed in terms of an equilibrium diagram between the neural and peripheral arcs. The neural arc represents the static input-output relationship between baroreceptor pressure input and efferent sympathetic nerve activity (SNA), whereas the peripheral arc represents that between SNA and arterial pressure (AP). In 8 anesthetized rabbits, we increased carotid sinus pressure stepwise from 40 to 160 mmHg in increments of 20 mmHg at one-minute intervals while measuring renal SNA and AP under control conditions and during the activation of the BJ reflex by intravenous administration of phenylbiguanide (PBG, 100 microg.kg(-1).min(-1)). The neural arc approximated a sigmoid curve whereas the peripheral arc approximated a straight line. PBG decreased AP at the operating point from -91.3 +/- 2.4 to -71.7 +/- 3.1 mmHg (P < 0.01), and attenuated the total loop gain at the operating point from -1.31 +/- 0.44 to -0.51 +/- 0.14 (P < 0.05). The equilibrium diagram indicated that PBG caused a parallel shift of the neural arc toward lower SNA such that the maximum SNA was reduced to approximately 60% of control. PBG decreased neural and peripheral arc gains at the operating point to approximately 43% and 77%, respectively. In conclusion, the BJ reflex blunts arterial baroreflex via the shift of the neural arc toward lower SNA.     

Daytime variability of baroreflex function in patients with obstructive sleep apnoea: implications for hypertension

Obstructive events during sleep in patients with obstructive sleep apnoea (OSA) cause large alterations in blood pressure, and this may lead to changes in baroreflex function with implications for long-term blood pressure control. This study examined the daytime variations in the responses to carotid baroreceptor stimulation in OSA patients. We determined the cardiac and vascular responses every 3 h between 09.00 and 21.00 h in 20 patients with OSA, using graded suctions and pressures applied to a neck collar. These responses were plotted against estimated carotid sinus pressures and, from these plots, baroreflex sensitivities and operating points were taken as the maximal slopes and the corresponding carotid sinus pressures, respectively. We found that at 09.00 h, sensitivity for the control of vascular resistance was at its lowest (--1.2 +/- 0.2% mmHg(-1), compared with --1.9 +/- 0.3% mmHg(-1) at 12.00 h, P < 0.02) and operating point for control of mean arterial pressure was at its highest (101.1 +/- 5.8 mmHg, compared with 94.1 +/- 5.8 mmHg at 12.00 h, P < 0.05). This is in contrast to previous data from normal subjects, in whom sensitivity was highest and operating point lowest at 09.00 h. We suggest that the higher baroreflex sensitivity and lower operating point seen in the mornings in normal subjects may provide a protective mechanism against hypertension and that this protection is absent in patients with OSA. It is possible that the reduced reflex sensitivity and increased operating point in the mornings may actually promote hypertension.     

Reflex responses from the main pulmonary artery and bifurcation in anaesthetised dogs

This study was undertaken to determine the reflex cardiovascular and respiratory responses to discrete stimulation of pulmonary arterial baroreceptors using a preparation in which secondary modulation of responses from other reflexes was prevented. Dogs were anaesthetised with -chloralose, artificially ventilated, the chests widely opened and a cardiopulmonary bypass established. The main pulmonary arterial trunk, bifurcation and extrapulmonary arteries as far as the first lobar arteries on each side were vascularly isolated and perfused through the left pulmonary artery and drained via the right artery through a Starling resistance which controlled pulmonary arterial pressure. Pressures distending systemic baroreceptors and reflexogenic regions in the heart were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a vascularly isolated hind limb and to the remainder of the subdiaphragmatic systemic circulation, both of which were perfused at constant flows. Respiratory responses were assessed from recordings of efferent phrenic nerve activity. Increases in pulmonary arterial pressure consistently evoked increases in both perfusion pressures and in phrenic nerve activity. Both vascular and respiratory responses were obtained when pulmonary arterial pressure was increased to above about 30 mmHg. Responses increased at higher levels of pulmonary arterial pressures. In 13 dogs increases in pulmonary arterial pressure to 45 mmHg increased systemic perfusion pressure by 24 +/- 7 mmHg (mean +/- S.E.M.) from 162 +/- 11 mmHg. Setting carotid sinus pressure at different levels did not influence the vascular response to changes in pulmonary arterial pressure. The presence of a negative intrathoracic pressure of -20 mmHg resulted in larger vascular responses being obtained at lower levels of pulmonary arterial pressure. This indicates that the reflex may be more effective in the intact closed-chest animal. These results demonstrate that stimulation of pulmonary arterial baroreceptors evokes a pressor reflex and augments respiratory drive. This reflex is likely to be elicited in circumstances where pulmonary arterial pressure increases and the negative excursions of intrathoracic pressure become greater. They are likely, therefore, to be involved in the cardio-respiratory response to exercise as well as in pathological states such as pulmonary hypertension or restrictive or obstructive lung disease.     

The role of calcium antagonists in bronchial reactivity

Calcium (Ca) ions play an important pathophysiologic role in allergic reactions. Thus, mediator release from mast cells, synthesis of some newly formed chemical mediators, airway smooth muscle contraction, and nerve-impulse conduction are all dependent on the availability and flux of Ca ions. It is likely, therefore, that Ca antagonists would modify allergic bronchoconstriction. In vitro, Ca antagonists have been demonstrated to inhibit mediator release (histamine, slow-reacting substance of anaphylaxis, and platelet-activating factor) from mast cells, passively sensitized human lung fragments, and leukocytes. Ca antagonists have also been found to inhibit synthesis of leukotrienes in rat lungs and cyclooxygenase products in sheep, possibly by inactivating phospholipase A2 and/or 5-lipoxygenase. In addition, nifedipine, verapamil, and gallopamil have demonstrated inhibition of airway smooth muscle contractions to histamine, carbachol, and antigen in various species. In vivo effects of Ca antagonists are variable, depending on the species, experimental design, the stimulus or the agonist, and the Ca antagonist used. Animal studies have demonstrated the inhibition of histamine, methacholine, citric acid, and prostaglandin F2 alpha-induced bronchoconstriction in guinea pigs and dogs by intravenous nifedipine. In contrast, verapamil inhibited antigen-induced bronchoconstriction in allergic sheep without any effect on histamine- and carbachol-induced responses. Ca antagonists (nifedipine and verapamil) have been of limited value in human subjects and generally have no significant bronchodilating activity. Both nifedipine and verapamil prevent the exercise-induced asthma and partly attenuate the histamine and methacholine-induced bronchoconstriction. Oral nifedipine is generally more effective than oral verapamil against acute antigen-induced bronchoconstriction; however, this efficacy may be limited by systemic side effects. Inhaled Ca antagonists may be more effective and free of systemic side effects, as demonstrated by greater efficacy of inhaled verapamil. A new Ca antagonist, gallopamil (a methoxy derivative of verapamil), is being investigated as an aerosol, and preliminary studies in animals and humans have found it fourfold to seventeenfold more potent than verapamil. In sheep, gallopamil has been found to attenuate histamine, carbachol, and platelet-activating factor-induced bronchoconstriction, as well as to inhibit early and late-phase allergic airway responses. Studies in human subjects have also demonstrated the inhibition of antigen-induced bronchoconstriction by inhaled gallopamil, with efficacy comparable or better than cromolyn sodium.(ABSTRACT TRUNCATED AT 400 WORDS)     

Local metabolite accumulation augments passive muscle stretch-induced modulation of carotid-cardiac but not carotid-vasomotor baroreflex sensitivity in man.

We examined the effects of muscle mechanoreflex stimulation by passive calf muscle stretch, at rest and during concurrent muscle metaboreflex activation, on carotid baroreflex (CBR) sensitivity. Twelve subjects either performed 1.5 min one-legged isometric plantarflexion at 50% maximal voluntary contraction with their right or left calf [two ischaemic exercise (IE) trials, IER and IEL] or rested for 1.5 min [two ischaemic control (IC) trials, ICR and ICL]. Following exercise, blood pressure elevation was partly maintained by local circulatory occlusion (CO). 3.5 min of CO was followed by 3 min of CO with passive stretch (STR-CO) of the right calf in all trials. Carotid baroreflex function was assessed using rapid pulses of neck pressure from +40 to -80 mmHg. In all IC trials, stretch did not alter maximal gain of carotid-cardiac (CBR-HR) and carotid-vasomotor (CBR-MAP) baroreflex function curves. The CBR-HR curve was reset without change in maximal gain during STR-CO in the IEL trial. However, during the IER trial maximal gain of the CBR-HR curve was smaller than in all other trials (-0.34 +/- 0.04 beats min(-1) mmHg(-1) in IER versus -0.76 +/- 0.20, -0.94 +/- 0.14 and -0.66 +/- 0.18 beats min(-1) mmHg(-1) in ICR, IEL and ICL, respectively), and significantly smaller than in IEL (P < 0.05). The CBR-MAP curves were reset from CO values by STR-CO in the IEL and IER trials with no changes in maximal gain. These results suggest that metabolite sensitization of stretch-sensitive muscle mechanoreceptive afferents modulates baroreflex control of heart rate but not blood pressure.