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CARDIOVASCULAR |
1 Department of Physiology, Bristol Heart Institute, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, UK
2
Department of Anaesthesia, Bristol Royal Infirmary, Bristol BS2 8HW, UK
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Abstract |
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(Received 7 November 2006;
accepted after revision 7 December 2006;
first published online 14 December 2006)
Corresponding author A. E. Pickering: Department of Physiology, Bristol Heart Institute, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, UK. Email: tony.pickering{at}bristol.ac.uk
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Introduction |
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It is therefore interesting that in human disease states such as hypertension there can be isolated, specific deficits in either the vascular sympathetic (Jordan et al. 2000) or cardiac parasympathetic components of the baroreflex (Mancia & Mark, 1983; Grassi et al. 1998). The specificity of these deficits is mirrored in both the spontaneously hypertensive rat (SHR; Head & Adams, 1988; Dickhout & Lee, 1998) and the renal wrap model of hypertension (Vitela et al. 2005) which exhibit a selective attenuation of the parasympathetic limb of the baroreflex. Furthermore, under normal physiological circumstances, there is evidence for separate regulation of the baroreflex limbs, for example during exercise (Raven et al. 2006). The forgoing suggests that the efferent limbs of the baroreflex can be independently controlled, presumably through alterations in brainstem processing.
This study was triggered by our observation that it is possible to fully dissociate the non-cardiac sympathetic and cardiac baroreflex components in a decerebrate, artificially perfused rat (DAPR) preparation (Simms et al. 2004). This in situ approach allows the effect of precise, pressure stimuli to be examined on a range of sympathetic and parasympathetic nerve and end-organ responses without the need for anaesthesia, artificial ventilation or vagotomy (Pickering & Paton, 2006). The aim of this study was to explore this apparent difference in the pressure sensitivity of baroreflex regulation of sympathetic and parasympathetic activity in both normotensive and spontaneously hypertensive rat strains. Some of these data have been communicated previously in abstract form (Simms et al. 2004).
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Methods |
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WHBP. The rat was bisected subdiaphragmatically, immersed in carbogenated Ringer solution at 10°C, and suction-decerebrated precollicularly. After transfer to the recording chamber a double lumen cannula was inserted into the descending aorta for retrograde perfusion.
DAPR preparation. The stomach, intestines and spleen were ligated and removed via a midline laparotomy. After sternotomy the ribcage was retracted to allow access to the mediastinum. The animal was cooled by immersion in carbogenated Ringer solution at 10°C and decerebrated precollicularly. Once in the recording chamber a double lumen perfusion cannula was introduced into the ascending aorta, via an incision in the left ventricle, for anterograde perfusion.
In both preparations, after decerebration, anaesthesia was discontinued as the animal was insentient. Perfusion was reinstated using a peristaltic roller pump (Watson Marlow 505D) with a carbogenated Ringer solution at 32°C (for constituents, see below). The second lumen of the cannula was used to monitor aortic perfusion pressure. The pump head speed was controlled using custom-written scripts (Spike2 driving micro1401, Cambridge Electronic Design, Cambridge, UK) allowing the generation of flexible flow change protocols to alter perfusion pressure.
The phrenic nerve activity (along with ECG) was recorded via a suction electrode (filtered 80 Hz to 3 kHz). The baseline perfusate flow was adjusted until the respiratory motor pattern consisted of an augmenting burst discharge indicating eupnoea (Paton, 1996). In addition, vasopressin (200–400 pM) was added to the perfusate, as required, to increase vascular resistance and hence baseline perfusion pressure (Pickering & Paton, 2006). Instantaneous heart rate (HR) in beats per minute (bpm) was derived by triggering from the R wave of the ECG with a window discriminator.
Cardiorespiratory afferent stimulation
The baroreflex was activated by perfusion pressure challenges (generated by altering the perfusate flow). Initial studies used flow steps to increase perfusion pressure (by 30 mmHg over 1 s) from a range of different baseline pressures (30–80 mmHg, by adjusting the baseline flow). We also used flow ramps (typically from 0 to 3 x basal flow over 15–60 s) to change flow linearly and thus produce biphasic perfusion pressure challenges.
The peripheral chemoreceptors were stimulated with NaCN (0.01% solution; 100 µl intra-aortic bolus) to produce a submaximal bradycardia (Paton & Kasparov, 1999). Such activation of the peripheral chemoreceptor reflex produced an increase in central respiratory drive accompanied by bradycardia and an increase in sympathetic nerve activity. The activation of the peripheral chemoreflex provided a method to check that a vagal bradycardia could be evoked; this was particularly pertinent on the occasions when there was an absence of baroreflex bradycardia.
Nerve recordings
Nerve recordings were made using suction electrodes from the lower thoracic (non-cardiac) sympathetic chain (T8–13), renal, adrenal, inferior cardiac (ICN) and cardiac vagal (CVN) nerves. The identity of the latter two nerves was confirmed by electrical stimulation (1–4 s train at 30–50 Hz; pulses 1 ms x 10–20 V) of the distal end of the nerve to obtain tachycardia (ICN, see Boscan et al. 2001) or bradycardia (CVN, see Pickering et al. 2003). All the sympathetic nerves exhibited marked respiratory modulation of their activity and this was profoundly attenuated by an increase in perfusion pressure (to stimulate arterial baroreceptors). The CVN also exhibited respiratory modulation with bursts of activity in the post-inspiratory period. However, by contrast with the sympathetic outflows, the CVN showed increased discharge in response to pressor stimuli (see Pickering et al. 2003). Nerve recordings were AC amplified (custom built), filtered (100–2000 Hz), rectified and integrated.
Data analysis
The baroreflex response to perfusion pressure challenges was quantified using two different methods. For the transient pressor challenges (1 s), applied from a range of baseline pressures, the cardiac baroreflex gain was calculated from the ratio of 
Heart rate/Perfusion pressure (bpm mmHg–1; see Paton & Kasparov, 1999). Because the SNA showed respiratory modulation, the pressor challenges were applied during the same phase of the respiratory cycle (end-inspiration). The sympathetic baroreflex gain was calculated by ratioing the change in 
SNA during the perfusion pressure ramp against the average of two equivalent control periods of SNA taken from the corresponding phase of preceding respiratory cycles (expressed as percentage sympathoinhibition per millimetre of mercury; see Pickering et al. 2003).
In contrast, for the dynamic biphasic pressure ramps (over 30 s) a baroreflex–function curve (Kent et al. 1972) was constructed (for the heart rate (HR), SNA and/or CVN activity (CVNA)) by fitting a logistic sigmoid (Prism4, Graphpad, CA, USA):
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Significance of data was assessed using Student's two-tailed t test, ANOVA or Wilcoxon signed rank test as appropriate (Prism4). All values quoted are the mean ± S.E.M. and differences were considered significant at the 95% confidence limit.
Drugs and solutions
The composition of the modified Ringer solution was (mM): NaCl (125); NaHCO3 (24); KCl (5); CaCl2 (2·5); MgSO4 (1·25); KH2PO4 (1·25); dextrose (10); pH 7·35–7.4 after carbogenation. The perfusion solution also contained Ficoll 70 (1·25%) as an oncotic agent, and heparin (1 i.u. ml–1). All chemicals were from Sigma (UK).
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Results |
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In the DAPR preparation it was possible to evoke baroreflex sympathoinhibition, in response to a pressor challenge, without an associated baroreflex bradycardia (Fig. 1Aa, seen in 6/20 DAPR preparations). These preparations had relatively low baseline perfusion pressures (less than 60 mmHg) but were otherwise functionally normal with eupnoeic patterns of phrenic discharge, respiratory sinus arrhythmia and robust peripheral chemoreflex bradycardia (Figs 1 and 2) indicative of intact cardiac vagal reflex function. Importantly, by increasing the baseline pressure (by the addition of vasopressin to the perfusate at 200–400 pM) the baroreflex bradycardia could be reinstated (n = 4, Fig. 1B).
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Distinct pressure operating ranges of baroreflex sympathoinhibition and bradycardia
To guard against the possibility that this ability to dissociate the limbs of the baroreflex might be an anomalous feature of the DAPR preparation these experiments were systematically repeated in the WHBP where the ability to manipulate the perfusion pressure is facilitated by the smaller remaining vascular tree. The baroreflex was challenged with pressure ramps (30 mmHg x 1 s) from a series of different baseline perfusion pressures (30–80 mmHg, n = 9) and the associated baroreflex gains were derived. Baroreflex sympathoinhibition was observed from all of the baseline pressures. However, like the DAPR experiments, the cardiac component of the baroreflex was typically only seen with pulses from a baseline pressure of greater than 50 mmHg. This appeared to reflect a pressure threshold for activation of the cardiac baroreflex with pressure pulses peaking between 75 and 90 mmHg across different preparations (mean 83 ± 3 mmHg, n = 9). The cardiac baroreflex gain increased by over 6-fold when the pressure ramp crossed this apparent threshold (–0.3 ± 0.04 to –2.0 ± 0.3 bpm mmHg–1, P < 0.0005, n = 9). In contrast, the baroreflex sympathetic gain only increased by 
50% (–1.3 ± 0.1 to –2.0 ± 0.3% sympathoinhibition mmHg–1, P < 0.01).
Detailed examination of the arterial pressure–baroreflex gain relationship in the WHBP (Fig. 2B) showed that the cardiac baroreflex was right-shifted by 15–20 mmHg to a higher pressure range compared to the baroreflex sympathoinhibition. Hence the perfusion pressure at 50% of the maximum gain was 67 mmHg for sympathoinhibition versus 85 mmHg for the bradycardia. However, using this approach with static changes in baseline pressure, it was not possible to define the low pressure end of the baroreflex sympathoinhibition curve. This was because at baseline perfusion pressures of less than 30 mmHg (for periods of more than about 30 s) the phrenic and cardiorespiratory reflex activity in the WHBP was compromised, indicating inadequate perfusion of the brainstem.
Dynamic biphasic pressure ramps separate the parasympathetic and sympathetic baroreflex limbs
To explore the low-pressure end of the sympathetic baroreflex curve, we devised a biphasic flow protocol allowing pressure to be transiently lowered to 20–30 mmHg then ramped up over 30 s at a rate of 2–3 mmHg s–1 (Fig. 3A). This dynamic ramp protocol produced a graded activation of the sympathetic and cardiac baroreflex. By fitting baroreflex function curves to the data (Fig. 3C and D, Table 1) it was apparent that the non-cardiac sympathetic baroreflex is active over a lower-pressure range than the cardiac baroreflex (Pth 66 ± 1 versus 82 ± 5 mmHg, P < 0.02; PP50% 77 ± 3 versus 87 ± 4 mmHg, P < 0.001, n = 6).
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Cardiac parasympathetic versus cardiac and non-cardiac sympathetic baroreflex limbs
To address this issue, recordings were made from the CVN during pressure challenges. The evoked, graded bradycardia was mirrored by a ramp increase in the CVN activity (Fig. 4A, n = 4). The increase in CVN activity was well described by the logistic sigmoid baroreflex function curve and the Pth was similar to that for the cardiac baroreflex (Fig. 4B). This indicates that the graded heart rate changes are consequent upon similar changes in CVN activity.
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Having shown a difference in the function curves between the cardiac and non-cardiac sympathetic baroreflex we were interested to extend the comparison to end-organ sympathetic nerves. Therefore, we made simultaneous recordings of adrenal and renal nerves in the DAPR (Fig. 7, n = 4). These recordings showed similar patterns of baroreflex pressure sensitivity to the low thoracic chain with both the adrenal and renal SNA being strikingly inhibited prior to a significant change in heart rate (Fig. 7).
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Changes in parasympathetic and sympathetic baroreflex function curves in spontaneously hypertensive rats
It has previously been reported that the baroreflex resets to a higher pressure range in hypertension (Head & Adams, 1988; Dickhout & Lee, 1998; Grassi et al. 1998). Therefore we were interested to see if the sympathetic and parasympathetic components of the baroreflex were reset to an equal degree in WHBP of SHR. Compared to Wistar rats, the SHR showed a higher baseline perfusion pressure (80 ± 4 versus 56 ± 3 mmHg, P < 0.002, n = 6) and heart rate (347 ± 8 versus 293 ± 19, P < 0.05, n = 6) at the same perfusate flow (17 ml min–1, Table 1). The higher pressure in the SHR therefore reflects a greater baseline vascular resistance.
Like the Wistar rats, there were differences in SHR in the non-cardiac sympathetic compared to the cardiac baroreflex (respectively, Pth 70 ± 3 versus 104 ± 4 mmHg, P < 0.002; PP50% 84 ± 4 versus 113 ± 4 mmHg, P < 0.01, n = 6, Fig. 8). Interestingly, when compared to the Wistar rats, both the sympathetic and cardiac baroreflex function curves in the SHR showed a trend towards a higher pressure range (Wistar PP50% values of 77 ± 3 and 87 ± 4 mmHg versus SHR 84 ± 4 and 113 ± 4 mmHg, respectively). However, only the increase in the cardiac baroreflex reached statistical significance (P = 0.005, Tables 1 and Fig. 8C) indicating that the cardiac component of the baroreflex has reset to a higher pressure range in the juvenile SHR. It was also notable that the cardiac baroreflex gain was reduced 4-fold in the SHR (Table 1).
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Discussion |
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The arterial baroreflex has been extensively investigated since its description (Cyon & Ludwig, 1866) (> 2300 animal studies indexed in Medline), and it is surprising that the ability to disengage the two limbs has not been observed. This may reflect the fact that only a small proportion of studies have examined the input (arterial pressure) and output function (nerve activity or end-organ response) of both the parasympathetic and sympathetic baroreflex limbs simultaneously. This has often been because the in vivo approaches employed to study the baroreflex have been done in ‘open loop’ vagotomized animals, or in the presence of anaesthesia (see Shimokawa et al. 1998) or neuromuscular blocking agents that obtund the cardiac limb of the baroreflex. Consequently many studies have appeared to make an underlying assumption that monitoring a single baroreflex efferent limb allows inferences to be made about the global function of the baroreflex, despite previous cautions to the contrary (Sagawa, 1983).
Notwithstanding, several recent studies (Ling et al. 1998; Foley et al. 2001; Vitela et al. 2005; McDowall et al. 2006) in anaesthetized rodents have examined baroreflex sympathetic and heart rate responses and have shown no differences in the baseline baroreflex function parameters. Curiously, these same studies have shown a variety of physiological, pharmacological and genetic interventions to differentially modulate the limbs of the baroreflex (Ling et al. 1998; Foley et al. 2001; Vitela et al. 2005; McDowall et al. 2006) raising the issue of why, under baseline conditions, the two limbs are operating within similar parameters.
However, a recent study in conscious rats has indicated that the baroreflex function curve threshold and midpoint pressures were approximately 20 mmHg lower for renal sympathetic nerve activity compared to heart rate (Miki et al. 2003), although these authors did not comment or elaborate on the potential significance of this observation. These findings can also be tied in with earlier studies on dogs and humans (Glick & Braunwald, 1965) and rats (Stornetta et al. 1987) that have shown pharmacologically that the baroreflex heart rate response is predominantly vagal in the pressor direction and predominantly sympathetic in the depressor direction. This qualitative asymmetry may be explained by our observed differences in the pressure range of the baroreflex function curves with the sympathetic system operating over a lower range. Hence an interesting possibility is raised by our findings; in baroreflex studies in humans SNA correlates best with diastolic pressure whereas heart rate changes correlate with the systolic or mean pressures (Sundlof & Wallin, 1978; Eckberg et al. 1988; Ebert & Cowley, 1992). This finding may result from differences in the respective pressure operating ranges of the baroreflex limbs.
Previous human studies suggest that muscle vasoconstrictor SNA is sensitive to increases in arterial pressure that are without effect on heart rate (Eckberg et al. 1988; Rudas et al. 1999). This is mirrored by our ability to produce striking sympathoinhibition with small changes in perfusion pressure (10 mmHg pressor challenge from baseline – 50% less SNA). It is noteworthy that our pressure stimuli were generated by altering the perfusate flow, thus exposing the barosensors to increases in pressure and flow (a situation commonly seen in vivo). The carotid sinus baroreceptors in dogs are sensitized under conditions of increased flow and pressure (Hajduczok et al. 1988) such that they exhibit lower thresholds for discharge. Also, it has recently been reported that the long-term level of human SNA may be better related to the cardiac output rather than to arterial pressure (Charkoudian et al. 2005), suggesting that the SNA is regulated by a cardiac output-sensitive mechanism. Thus it could be hypothesized that our approach may detect a difference between the baroreflex limbs because the sympathetic system is sensitive to both pressure and flow (this intriguing possibility could be tested using in situ preparations as flow and pressure can be independently controlled).
Our use of artificially perfused preparations has afforded the ability to explore the low-pressure end of the baroreflex relationship in detail. By comparison, the commonly used in vivo approach to assess the baroreflex employs administration of vasodilator followed by vasoconstrictor to manipulate arterial pressure and explore the operating range of the baroreflex (e.g. Ebert & Cowley, 1992). However, there are limits as to how far the systemic pressure can be lowered because of the unwanted effects of CNS/cardiac ischaemia. There may also be direct drug effects on the vessels at the baroreceptor sites and on the heart/brain that may alter the response. An alternative approach isolates and exposes a single baroreceptor region (e.g. carotid sinus) to a wide range of pressures without interference from the other baroreceptors (‘open loop’ following denervation, see Shoukas et al. 1991). However, such isolated carotid sinus experiments allow the effects to be measured from only one of the baroafferent sites and it is known that the effect of each of these afferent sites can be different (Dworkin et al. 2000) and can sum in a non-linear fashion (Sagawa, 1983). Our in situ approach allows precise control of both baseline and stimulus pressures, independent of the cardiac output, and we are able to compensate for changes in the vascular resistance by altering perfusate flow. Thus, we can repeatedly apply defined stimuli to all four barosensor sites and quantify the parameters of the baroreflex response in terms of nerve activity and end-organ responses (heart rate and vascular resistance). Furthermore, because we continuously monitor phrenic nerve activity we can detect (and rectify) signs of brainstem ischaemia
In our in situ preparations, it should be noted that there is almost no arterial pulse wave as the preparation is perfused independently, from a peristaltic pump, bypassing the cardiac output. The pressure pulse wave in vivo phasically activates the baroreceptors and there is evidence that it augments baroreflex-mediated sympathoinhibition (Ead et al. 1952; James & Daly, 1970; Chapleau et al. 1989) (but not heart rate changes: Ead et al. 1952). Furthermore, the sympathetic outflow shows a pulse-related modulation of activity that is a manifestation of this phasic baroreflex activation by the pressure pulse (Adrian et al. 1932; Habler et al. 1994; Malpas, 1998). This raises the issue of whether the pulselessness of the artificially perfused in situ preparation is leading to non-physiological stimulation of the baroafferents and hence producing misleading results. In addressing this issue it is important to emphasize that in our study we have obtained similar results using both brief, phasic pressure pulses (rising phase 1–2 s) and also slower pressure ramps (over 30 s) and in both cases have shown clear differences in the pressure sensitivity of the cardiac and non-cardiac sympathetic baroreflex limbs under both conditions. It is also worth noting that previous studies of the baroreflex in vivo have obtained baroreflex function curves using averaged changes in mean pressure rather than instantaneous pulsatile pressure, thus they have taken little account of the variation in pressure pulsatility (Ling et al. 1998; Foley et al. 2001; Vitela et al. 2005; McDowall et al. 2006). In support of our findings, a recent study in conscious rats has described a similar difference in the operating range of the renal sympathetic and heart rate baroreflex (Miki et al. 2003), suggesting that our in situ observations are indeed comparable with those seen in vivo.
In SHR WHBP (4–6 weeks of age) the baseline perfusion pressure and resting heart rate were elevated (compared to Wistars). Similar findings have been reported with SHR in vivo showing significant increases in arterial pressure from 4 weeks of age and heart rate from 2 weeks of age (Dickhout & Lee, 1998). We show that in the juvenile SHR there is an exaggerated difference in the pressure operating range of the limbs of the baroreflex as the cardiac limb has selectively reset to higher pressures. This is somewhat surprising given the well-known resetting of the peripheral baroafferents seen in the SHR (Andresen et al. 1978; Chapleau et al. 1988). However, our findings agree with previous studies in SHR that show a selective change in the cardiac parasympathetic component of the heart rate response with preservation of the sympathetic baroreflex (Head & Adams, 1988, 1992; Salgado et al. 2006). Thus these juvenile SHR in situ show increased vascular resistance, heart rate and an underlying resetting of the cardiac baroreflex to higher pressures. It is interesting to speculate that this selective resetting of the cardiac baroreflex may permit the increase in heart rate that precedes (and predicts) the development of hypertension in SHR (Dickhout & Lee, 1998). These data also further demonstrate the similarity between the SHR and human hypertension with selective alterations of the cardiac (parasympathetic) component of the baroreflex with a shift to higher pressures, a decreased gain and a reduced range (Mancia & Mark, 1983; Grassi et al. 1998).
The location within the baroreflex arc where the differential control of the baroreflex limbs originates remains to be determined. In particular, it is interesting to consider whether the two limbs of the reflex receive the same information from the baroreceptors or if there is segregation and differential processing of this afferent traffic before the split downstream of the nucleus tractus solitarii (NTS). One plausible explanation of our findings is that the processed baro-output from the NTS may be more effective at exciting the neurones of the caudal ventrolateral medulla (sympathetic limb) than the cardiac vagal preganglionic neurones (parasympathetic) and thus the different thresholds reflect the differences in the integrative properties of these groups of neurones. Under this model, both limbs of the reflex would receive the same information from the NTS. However, there are indications that differential processing of the baroreflex information may originate in the periphery, such as the observation of differences in the pressure responsiveness of the aortic versus the carotid baroreceptors in dogs (Donald & Edis, 1971) and the observation of a dominant role for the aortic baroreceptors in the cardiac component of the reflex in conscious rats (Dworkin et al. 2000). There are also differences in the heart rate and vascular responses to selective A- and C-fibre stimulation of baroreflex afferents such that A-fibres appear critical in the generation of baroreflex heart rate responses (Fan et al. 1999). Additionally, within the nucleus of the solitary tract, barosensitive neurones exhibit different single cell responses (Zhang & Mifflin, 2000; Paton et al. 2001) and the demonstration that the limbs of the baroreflex have differential pharmacological sensitivity (e.g. Pickering et al. 2003; Simms et al. 2006). These lines of evidence suggest that the transduced pressure information may be specifically tailored for the output limbs of the baroreflex by the NTS, or perhaps even earlier in the reflex arc, in the organization and functional properties of the baroafferents.
Through the use of in situ artificially perfused rat preparations we have shown clear differences in the pressure operating ranges of the sympathetic and parasympathetic limbs of the baroreflex, with the sympathetic limb being active at lower pressures. This is exaggerated in the SHR model of hypertension with a selective increase in the pressure range of the cardiac baroreflex. These observations indicate that there is a functional pressure hierarchy for recruitment of the sympathetic and parasympathetic baroreflex limbs that extends the previous observation of the non-uniform baroreflex effects on the sympathetic outflows to different vascular beds (Ninomiya et al. 1971). Given the ability to independently modulate the limbs of the baroreflex under a range of physiological and pathological conditions (Mancia & Mark, 1983; Grassi et al. 1998; Ling et al. 1998; Jordan et al. 2000; Foley et al. 2001; Miki et al. 2003; Vitela et al. 2005; McDowall et al. 2006; Raven et al. 2006) it seems likely that it is possible to dynamically restructure this functional hierarchy. This provides considerable flexibility of baroreflex response pattern with the ability to favour changes in flow or pressure to particular vascular beds according to the specific physiological circumstance.
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References |
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-200 ms). Aa, application of a pressor challenge (bar) evoked baroreflex sympathoinhibition without a bradycardia. Ab, by contrast, activation of the peripheral chemoreflex (NaCN 0.01%, 0.1 ml) evoked an increase in respiratory frequency, sympathetic nerve activity and pertinently a bradycardia, indicating that the reflex cardiac vagal outflow to the heart was intact (note change of scale in heart rate trace). B, the addition of arginine-vasopressin (AVP, 400 pM) to the perfusate increased the baseline perfusion pressure by 20 mmHg (arrow). From this higher baseline (10 min later) an equivalent pressor challenge produced a marked bradycardia associated with a similar degree of sympathoinhibition to that in Aa.
) and sympathetic (
) gains were normalized against the maximum within each preparation (n = 9) and the pooled data were plotted against the peak perfusion pressure (mean ± S.E.M., n > 4 for each point). This showed that the normalized sympathetic gain was larger than the cardiac gain over the range 60–95 mmHg (*P < 0.05, **P < 0.01) and the degree of shift in the pressure–gain relationship was indicated by the pressure at 50% maximum gain (sympathoinhibition 67 mmHg versus bradycardia 85 mmHg, dotted lines).
) and heart rate (
) and heart rate (
) data (from A). The threshold for the cardiac baroreflex (79 mmHg) was similar to that of the CVN (80 mmHg). (R2 > 0.90, 95% confidence intervals dotted; parasympathetic function curve parameters: Pth 80 mmHg, PP50% 90 mmHg, Psat 101 mmHg, gain 0.14 µV mmHg–1; cardiac function curve parameters: Pth 79 mmHg, PP50% 84 mmHg, Psat 89 mmHg, gain 22 bpm mmHg–1.)
