Baroreflex Changes Research Articles

Modeling and Analysis of Central and Peripheral Autonomic Contributions to Decreased Cardiac Vagal Tone Following Myocardial Infarction

Loss of cardiac function following myocardial infarction is accompanied by neural adaptation in baroreflex systems that are compensatory in the short term but then become associated with long-term disease progression. A hallmark of these baroreflex changes is decreased vagal tone. The closed-loop feedback structure of the baroreflexes confounds the source of decreased vagal tone following myocardial infarction (MI). We recognize that in a feedback network causality is distributed in the network interactions, and so explore the effects of MI on the potential contribution to vagal withdrawal of each neural component of our previously published closed-loop baroreflex computational model. The model is composed of differential equations representing the blood flow through various body compartments and sigmoidal functions to represent the saturating firing behavior of neurons. Neuronal adaptations leading to decreased vagal activity could occur in various neuronal groups located centrally in the brainstem. Adaptations could also occur peripherally at the baroreceptors or the heart’s “little brain”, the intrinsic cardiac nervous system. We developed five alternative models to reflect these hypotheses. Of the alternative models, only the model representing adaptation in the baroreceptors predicted both physiological baroreflex function and a decrease in vagus nerve activity. These findings suggest that decreased vagal activity after myocardial ischemia may be due, at least in part, to a decrease in baroreceptor sensitivity. We also link these model predictions with experimental evidence from the literature. NIH U01-HL133360, NIH OT2-OD030534, NSF 1940700, and NSF OAC-1919839. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Prolonged unloading of the cardiovascular system during bedrest and spaceflight weakens neural coupling between blood pressure and heart rate

Impaired baroreflex control following bedrest and spaceflight severely affects rate of recovery and return to ambulatory tasks. Post-bedrest/spaceflight orthostatic intolerance remains a major concern for bedrest confined older patients and for astronauts on long-duration missions. Here, we investigated how baroreflex changes following cardiovascular unloading were associated with autonomic neural coupling between blood pressure and heart rate in returning astronauts and in healthy participants who had undergone prolonged bedrest. Cardiovascular data collected from 27 shuttle astronauts (8–16 days) were compared with 19 head-down tilt bedrest (HDBR, 60 days) volunteers. In each group, beat-by-beat systolic blood pressure (SBP) and heart period (R-to-R intervals, RR) were collected simultaneously during a supine-to-stand test (5–10 min) conducted around 10 days before launch or HDBR and within 120 min of landing or exiting HDBR. Indices characterizing interaction time (fraction time active), response gain (gain), and control directionality (causality) between SBP and RR (SBP→RR: neural reflex, and RR→SBP: mechanical coupling) during standing were derived from the beat-by-beat data. Following spaceflight, cardiac baroreflex fraction time active was reduced along with neural reflex causality, with much larger reductions seen with HDBR. No change in mechanical causality pre-post flight or HDBR was observed; however, comparison of male and female astronauts indicated that neural and mechanical causality were both lower in females. Altogether, these findings suggest that changes in blood pressure regulation after bedrest and spaceflight are primarily reflex/neurally mediated and provides a target for therapeutic approaches to cardiovascular deconditioning.

Cardiovascular Autonomic Regulation, ETCO2 and the Heart Rate Response to the Tilt Table Test in Patients with Orthostatic Intolerance.

Chronic orthostatic intolerance (COI) is defined by changes in heart rate (HR), blood pressure (BP), respiration, symptoms of cerebral hypoperfusion and sympathetic overactivation. Postural tachycardia syndrome (POTS) is the most common form of COI in young adults and is defined by an orthostatic increase in heart rate (HR) of ≥ 30bpm in the absence of orthostatic hypotension. However, some patients referred for evaluation of COI symptoms do not meet the orthostatic HR response criterion of POTS despite debilitating symptoms. Such patients are ill defined, posing diagnostic and therapeutic challenges. This study explored the relationship among cardiovascular autonomic control, the orthostatic HR response, EtCO2 and the severity of orthostatic symptoms and fatigue in patients referred for evaluation of COI. Patients (N = 108) performed standardized testing protocol of the Autonomic Reflex Screen and completed the Composite Autonomic Symptom Score (COMPASS-31) and the Fatigue Severity Scale (FSS). Greater severity of COI was associated with younger age, larger phase IV amplitude in the Valsalva maneuver and lower adrenal baroreflex sensitivity. Greater fatigue severity was associated with a larger reduction in ETCO2 during 10min of head-up tilt (HUT) and reduced low-frequency (LF) power of heart rate variability. This study suggests that hemodynamic changes associated with the baroreflex response and changes in EtCO2 show a stronger association with the severity of orthostatic symptoms and fatigue than the overall orthostatic HR response in patients with COI.

The differential modulation of the baroreflex control mechanism in fight, flight or freeze behaviour.

The differential modulation of the baroreflex control mechanism in fight, flight or freeze behaviour.

Exaggerated pressor and sympathetic nerve responses during spontaneously‐occurring motor activity in decerebrate spontaneously hypertensive rats

Stimulation of the mesencephalic locomotor region (a putative component of the central command pathway) has been shown to elicit exaggerated pressor and sympathetic nerve responses in decerebrate spontaneously hypertensive rats (SHR) as compared to normotensive Wister-Kyoto rats. This finding suggests that central command activity and/or influence on caudal vasomotor centers may be augmented in hypertension. In the normotensive decerebrate rat model, mean arterial pressure (MAP) and sympathetic nerve activity are known to increase during intermittent bouts of spontaneous motor activity. Moreover, evidence suggests that simulated central command influences at the brainstem may evoke these pressor and sympathetic responses. However, it remains unknown whether these spontaneous changes in cardiovascular hemodynamics are altered with the pathogenesis of hypertension. Based on this background, we hypothesized that the pressor and sympathetic nerve responses during spontaneously-occurring motor activity are exaggerated in hypertension. MAP, renal sympathetic nerve activity (RSNA), and tibial nerve discharge were measured in decerebrate SHR (n=8) and normotensive Sprague-Dawley (SD) rats (n=6). The present study aimed to compare resting baroreflex changes in RSNA (in response to pharmacological alterations in MAP) and central command-evoked responses in MAP and RSNA during spontaneously-occurring motor activity between SHR and normotensive SD. Results demonstrated that the baroreflex-mediated RSNA response was not different between SHR and SD. In both SHR and SD, abrupt, spontaneous increases in RSNA were synchronized with tibial motor discharge and followed by a rise in MAP. These potentially central command-evoked increases in MAP and RSNA were greater in SHR than SD. Phenylephrine-induced elevations in MAP did not suppress the central command-induced RSNA increase in SHR, whereas it abolished the rise in RSNA in SD. Taken together, it is concluded that 1) the arterial baroreflex is operative during resting conditions in SHR as well as SD; 2) the pressor and sympathetic nerve responses during spontaneously-occurring motor activity are exaggerated in hypertensive rats; and 3) exaggerated RSNA responses in SHR may be induced along a central command pathway independent of the arterial baroreflex and/or as a result of central command-induced inhibition of the arterial baroreflex itself.

Role of angiotensin receptors in the medial amygdaloid nucleus in autonomic, baroreflex and cardiovascular changes evoked by chronic stress in rats.

This study investigated the role of AT1 , AT2 and Mas angiotensinergic receptors within the MeA in autonomic, cardiovascular and baroreflex changes evoked by a 10-day (1hr daily) repeated restraint stress (RRS) protocol. Analysis of cardiovascular function after the end of the RRS protocol indicated increased values of arterial pressure, without heart rate changes. Arterial pressure increase was not affected by acute MeA treatment after the RRS with either the selective AT1 receptor antagonist losartan, the selective AT2 receptor antagonist PD123319 or the selective Mas receptor antagonist A-779. Analysis of heart rate variability indicated that RRS increased the sympathetic tone to the heart, which was inhibited by MeA treatment with either losartan, PD123319 or A-779. Baroreflex function assessed using the pharmacological approach via intravenous infusion of vasoactive agents revealed a facilitation of tachycardia evoked by blood pressure decrease in chronically stressed animals, which was inhibited by MeA treatment with losartan. Conversely, baroreflex responses during spontaneous fluctuations of blood pressure were impaired by RRS, and this effect was not affected by injection of the angiotensinergic receptor antagonists into the MeA. Altogether, the data reported in the present study suggest an involvement of both angiotensinergic receptors present in the MeA in autonomic imbalance evoked by RRS, as well as an involvement of MeA AT1 receptor in the enhanced baroreflex responses during full range of blood pressure changes. Results also indicate that RRS-evoked increase in arterial pressure and impairment of baroreflex responses during spontaneous variations of arterial pressure are independent of MeA angiotensinergic receptors.

Role of hippocampal nitrergic neurotransmission in behavioral and cardiovascular dysfunctions evoked by chronic social stress

Increased nitric oxide (NO) levels have been identified in the hippocampus of animals subjected to social isolation. However, a role of this change in behavioral and physiological changes evoked by isolation has never been evaluated. Thus, this study investigated the involvement of nitrergic neurotransmission acting via the neuronal isoform of nitric oxide synthase (nNOS) within the dorsal hippocampus in behavioral and cardiovascular changes in isolated reared rats. For this, male rats were isolated from weaning at 21 days postnatal for 40 days. We identified that social isolation increased hippocampal NO formation and nNOS expression. Besides, anxiogenic- and depressive-like effect identified in isolated animals were not affected by intra-hippocampal microinjection of either the NO scavenger carboxy-PTIO or the selective nNOS inhibitor Nω-Propyl-l-arginine (NPLA). Isolation also increased basal arterial pressure, impaired the baroreflex function and decreased the tachycardia to restraint stress. The effects in restraint-evoked tachycardia were inhibited by hippocampal treatment with either carboxy-PTIO or NPLA. Intra-hippocampal administration of either carboxy-PTIO or NPLA also enhanced the pressor response to restraint in isolated, but not in control animals. Taken together, these findings indicate that increased NO release within the dorsal hippocampus is involved in impairment of cardiovascular responses to a novel stressor, but not in behavioral effects and baroreflex changes, evoked by social isolation. Furthermore, exposure to this stressor evokes the emergence of an inhibitory role of hippocampal nNOS activation in cardiovascular changes to a novel stressor, which might constitute a prominent adaptive response.

Involvement of CRF1 receptors in bed nucleus of stria terminalis (BNST) on baroreflex responses in chronically stressed rats

INTRODUCTIONStudies suggest the involvement of CRF receptors in bed nucleus of the stria terminalis (BNST) on cardiovascular responses in acute stress. Data from our group had demonstrated that the expression of CRF1 receptors within the BNST is decreased in animals exposed to chronic variable stress (CVS). Nevertheless, an involvement of BNST CRF neurotransmission on cardiovascular changes evoked by CVS has never been investigated.AIMTo evaluate the involvement of CRF1 receptor in the BNST on baroreflex changes evoked by CVS in rats.METHODOLOGYMale Wistar rats (250g) were submitted to stereotaxic surgery for implantation of cannulas into the BNST. After 4 days of recovery, the animals were exposed to a CVS protocol for 10 days. After the last session, the rats had the femoral artery and vein cannulated for cardiovascular record and drug infusion, respectively. Twenty‐four hours later, the experiments were performed. Baroreflex function was assessed by evoking changes on arterial pressure throughout intravenous infusions of phenylephrine and sodium nitroprusside, which evoke pressor and depressor effects, respectively. Baroreflex activity was evaluated in both control rats and animals subjected to ECV protocol before and after bilateral microinjection of the selective CRF1 antagonist CP376395 (5nmol/100nL) into the BNST.RESULTSComparison of values before BNST treatment revealed that ECV decreased the bradycardiac response evoked by blood pressure increase (−48±10 vs −114±23 bpm, P<0.03). Moreover, bilateral microinjection of CP376395 into the BNST decreased reflex bradycardia in control group (−51±13 vs −114±23 bpm, P<0.02), but not in animals subjected to ECV (−51±10 vs −48±10 bpm, P>0.05). The tachycardia evoked by blood pressure decrease was also decreased following ECV (57±5 vs 97±11 bpm, P<0.05). The BNST treatment with CP376395 decreased the tachycardiac response in control animals (50±9 vs 97±11 bpm, P<0.001), but without affecting this response in CVS rats (52±5 vs 57±5 bpm, P>0.05).CONCLUSIONThe impairment of baroreflex function evoked by CVS is related to decreased control of this reflex cardiovascular by CRF1 receptor in the BNST.Support or Funding InformationFINANCIAL SUPPORT: FAPESPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cardiovascular alterations at different stages of hypertension development during ethanol consumption: Time-course of vascular and autonomic changes

The aim of the present work was to establish a time-course correlation between vascular and autonomic changes that contribute to the development of hypertension during ethanol ingestion in rats. For this, male Wistar rats were subjected to the intake of increasing ethanol concentrations in their drinking water during four weeks. Ethanol effects were investigated at the end of each week. Mild hypertension was already observed at the first week of treatment, and a progressive blood pressure increase was observed along the evaluation period. Increased pressor response to phenylephrine was observed from first to fourth week. α1-adrenoceptor protein in the mesenteric bed was enhanced at the first week, whereas β2-adrenoceptor protein in the aorta was reduced after the second week. In the third week, ethanol intake facilitated the depressor response to sodium nitroprusside, whereas in the fourth week it reduced nitrate content in aorta and increased it plasma. The bradycardic component of the baroreflex was impaired, whereas baroreflex tachycardia was enhanced at the third and fourth weeks. AT1A receptor and C-type natriuretic peptide (CNP) mRNAs in the nucleus tractus solitarius were increased at the fourth week. These findings suggest that increased vascular responsiveness to vasoconstrictor agents is possibly a link factor in the development and maintenance of the progressive hypertension induced by ethanol consumption. Additionally, baroreflex changes are possibly mediated by alterations in angiotensinergic mechanisms and CNP content within the brainstem, which contribute to maintaining the hypertensive state in later phases of ethanol ingestion. Facilitated vascular responsiveness to nitric oxide seems to counteract ethanol-induced hypertension.

Role of the bed nucleus of the stria terminalis in cardiovascular changes following chronic treatment with cocaine and testosterone: A role beyond drug seeking in addiction?

Neural plasticity has been observed in the bed nucleus of the stria terminalis (BNST) following exposure to both cocaine and androgenic–anabolic steroids. Here we investigated the involvement of the BNST on changes in cardiovascular function and baroreflex activity following either single or combined administration of cocaine and testosterone for 10 consecutive days in rats. Single administration of testosterone increased values of arterial pressure, evoked rest bradycardia and reduced baroreflex-mediated bradycardia. These effects of testosterone were not affected by BNST inactivation caused by local bilateral microinjections of the nonselective synaptic blocker CoCl2. The single administration of cocaine as well as the combined treatment with testosterone and cocaine increased both bradycardiac and tachycardiac responses of the baroreflex. Cocaine-evoked baroreflex changes were totally reversed after BNST inactivation. However, BNST inhibition in animals subjected to combined treatment with cocaine and testosterone reversed only the increase in reflex tachycardia, whereas facilitation of reflex bradycardia was not affected by local BNST treatment with CoCl2. In conclusion, the present study provides the first direct evidence that the BNST play a role in cardiovascular changes associated with drug abuse. Our findings suggest that alterations in cardiovascular function following subchronic exposure to cocaine are mediated by neural plasticity in the BNST. The single treatment with cocaine and the combined administration of testosterone and cocaine had similar effects on baroreflex activity, however the association with testosterone inhibited cocaine-induced changes in the BNST control of reflex bradycardia. Testosterone-induced cardiovascular changes seem to be independent of the BNST.

Relative contributions of the thalamus and the paraventricular nucleus of the hypothalamus to the cardiac sympathetic afferent reflex

The cardiac sympathetic afferent reflex (CSAR) is induced by stimulating the cardiac sympathetic afferents, which evokes increases in sympathetic outflow and arterial pressure. In the present study, we attempted to identify the contribution of thalamic and hypothalamic nuclei involved in the CSAR. First, we observed that there was an increase in the number of c-Fos-labeled cells in the paraventricular nucleus (PVN) (190 ± 18 vs. 101 ± 15; P < 0.05), the paraventricular nucleus of the thalamus (PVT) (239 ± 23 vs. 151 ± 15; P < 0.05), and the mediodorsal thalamic nucleus (MD) (92 ± 9 vs. 63 ± 6; P < 0.05) following epicardial application of bradykinin (BK) compared with the control group (P < 0.05). Second, using extracellular single-unit recording, we found 25% of spontaneously active neurons in the thalamus were stimulated by epicardial application of BK or capsaicin in intact rats. However, 24% of spontaneously active neurons in the thalamus were still stimulated by epicardial application of BK or capsaicin despite vagotomy and sinoaortic denervation. None of the neurons in the thalamus responded to baroreflex changes in arterial pressure, induced by intravenous injection of phenylephrine or sodium nitroprusside. The CSAR was inhibited by microinjection of muscimol or lidocaine into the PVN. However, it was not inhibited or blocked by microinjection of muscimol or lidocaine into the thalamus. Taken together, these data suggest that the thalamus, while activated, is not critical for autonomic adjustments in response to activation of the CSAR. On the other hand, the PVN is critically involved in the central pathway of the CSAR.

Mindfulness meditation, well-being, and heart rate variability: A preliminary investigation into the impact of intensive Vipassana meditation

Mindfulness meditation has beneficial effects on brain and body, yet the impact of Vipassana, a type of mindfulness meditation, on heart rate variability (HRV) – a psychophysiological marker of mental and physical health – is unknown. We hypothesised increases in measures of well-being and HRV, and decreases in ill-being after training in Vipassana compared to before (time effects), during the meditation task compared to resting baseline (task effects), and a time by task interaction with more pronounced differences between tasks after Vipassana training. HRV (5-minute resting baseline vs. 5-minute meditation) was collected from 36 participants before and after they completed a 10-day intensive Vipassana retreat. Changes in three frequency-domain measures of HRV were analysed using 2 (Time; pre- vs. post-Vipassana)×2 (Task; resting baseline vs. meditation) within subjects ANOVA. These measures were: normalised high-frequency power (HF n.u.), a widely used biomarker of parasympathetic activity; log-transformed high frequency power (ln HF), a measure of RSA and required to interpret normalised HF; and Traube–Hering–Mayer waves (THM), a component of the low frequency spectrum linked to baroreflex outflow. As expected, participants showed significantly increased well-being, and decreased ill-being. ln HF increased overall during meditation compared to resting baseline, while there was a time∗task interaction for THM. Further testing revealed that pre-Vipassana only ln HF increased during meditation (vs. resting baseline), consistent with a change in respiration. Post-Vipassana, the meditation task increased HF n.u. and decreased THM compared to resting baseline, suggesting post-Vipassana task-related changes are characterised by a decrease in absolute LF power, not parasympathetic-mediated increases in HF power. Such baroreflex changes are classically associated with attentional load, and our results are interpreted in light of the concept of ‘flow’ — a state of positive and full immersion in an activity. These results are also consistent with changes in normalised HRV reported in other meditation studies.

Control of cardiovascular variability during undisturbed wake-sleep behavior in hypocretin-deficient mice

The central neural mechanisms underlying differences in cardiovascular variability between wakefulness, non-rapid-eye-movement sleep (NREMS), and rapid-eye-movement sleep (REMS) remain poorly understood. These mechanisms may involve hypocretin (HCRT)/orexin signaling. HCRT signaling is linked to wake-sleep states, involved in central autonomic control, and impaired in narcoleptic patients. Thus, we investigated whether HCRT signaling plays a role in controlling cardiovascular variability during spontaneous behavior in HCRT-deficient mice. HCRT-ataxin3 transgenic mice lacking HCRT neurons (TG), knockout mice lacking HCRT peptides (KO), and wild-type controls (WT) were instrumented with electrodes for sleep recordings and a telemetric blood pressure transducer. Fluctuations of systolic blood pressure (SBP) and heart period (HP) during undisturbed wake-sleep behavior were analyzed with the sequence technique, cross-correlation functions, and coherent averaging of SBP surges. During NREMS, all mice had lower SBP variability, greater baroreflex contribution to HP control at low frequencies, and greater amplitude of the central autonomic and baroreflex changes in HP associated with SBP surges than during wakefulness. During REMS, all mice had higher SBP variability and depressed central autonomic and baroreflex HP controls relative to NREMS. HP variability during REMS was higher than during NREMS in WT only. TG and KO also had lower amplitude of the cardiac baroreflex response to SBP surges during REMS than WT. These results indicate that chronic lack of HCRT signaling may cause subtle alterations in the control of HP during spontaneous behavior. Conversely, the integrity of HCRT signaling is not necessary for the occurrence of physiological sleep-dependent changes in SBP variability.

Baroreflex changes only stressed volume not the slope of the venous return surface in anesthetized dogs

Baroreflex changes only stressed volume not the slope of the venous return surface in anesthetized dogs

Repeated Cisplatin Treatments inhibit Gastrointestinal Motility and Induces Baroreflex Changes and Mechanical Hyperalgesia in Rats

Cisplatin is a chemotherapy agent known for its neurotoxicity. We evaluated the effect of cisplatin on the gastric emptying (GE), gastrointestinal (GI) transit of liquid, baroreflex function, thermal, and mechanical withdrawal latencies in rats. Cisplatin increased the GE of liquid with doses ≥2 mg.kg−1 by 59.7–77.4%. This GE delay was not present two weeks after the treatment with five doses of cisplatin at 1 mg.kg−1. Cisplatin also enhanced baroreflex gain possibly by increasing sympathetic activity. Our results demonstrated that cisplatin (2–10 mg.kg−1) causes autonomic neuropathy with GI and baroreflex changes and mechanical but not thermal hyperalgesia in rats.

Baroreflex changes only stressed volume not the slope of the venous return surface

Background Although Guyton established the framework of circulatory equilibrium by cardiac output (CO) and venous return (VR), the contribution of the left ventricle (LV) was obscured. To clarify this, we defined the VR as a function of both right (PRA) and left (PLA) atrial pressures, formulated as VRS=V/W–(GSPRA+GPPLA) (VRS: VR surface, V/W: maximum VR, GS: systemic and GP: pulmonary venous conductance) and demonstrated the uniformity of those parameters across animals (AJP 2004, 2005). However how baroreflex impacts the VR remains unknown. Methods/Results In 6 anesthetized, vagotomized dogs, we isolated carotid sinuses and controlled carotid sinus pressure. We replaced both ventricles by roller pumps. We first matched CO of two pumps. We then momentarily changed CO of either one of them to shift blood between the pulmonary and systemic circulations. We shifted the volume at least 6 times. We ran the same protocol at CSP of 100 or 120 mmHg. We applied multivariate regression and determined V/W, GP, and GS. The coefficient of determination ranged 0.89–0.99 indicating the flatness of the VRS. Decreasing CSP increased V/W (246±149 vs. 291±130 ml/kg/min, p<0.01), whereas did not change GS (22±9 vs. 25±9 ml/kg/min/mmHg, ns) or GP (3.5±2 vs. 3.9±1.8 ml/kg/min/mmHg, ns). Conclusions Baroreflex changed the maximum VR, thereby stressed volume significantly, but did not change the slope of the VRS.

Role of ionotropic GABA, glutamate and glycine receptors in the tonic and reflex control of cardiac vagal outflow in the rat

BackgroundCardiac vagal preganglionic neurons (CVPN) are responsible for the tonic, reflex and respiratory modulation of heart rate (HR). Although CVPN receive GABAergic and glutamatergic inputs, likely involved in respiratory and reflex modulation of HR respectively, little else is known regarding the functions controlled by ionotropic inputs. Activation of g-protein coupled receptors (GPCR) alters these inputs, but the functional consequence is largely unknown. The present study aimed to delineate how ionotropic GABAergic, glycinergic and glutamatergic inputs contribute to the tonic and reflex control of HR and in particular determine which receptor subtypes were involved. Furthermore, we wished to establish how activation of the 5-HT1A GPCR affects tonic and reflex control of HR and what ionotropic interactions this might involve.ResultsMicroinjection of the GABAA antagonist picrotoxin into CVPN decreased HR but did not affect baroreflex bradycardia. The glycine antagonist strychnine did not alter HR or baroreflex bradycardia. Combined microinjection of the NMDA antagonist, MK801, and AMPA antagonist, CNQX, into CVPN evoked a small bradycardia and abolished baroreflex bradycardia. MK801 attenuated whereas CNQX abolished baroreceptor bradycardia. Control intravenous injections of the 5-HT1A agonist 8-OH-DPAT evoked a small bradycardia and potentiated baroreflex bradycardia. These effects were still observed following microinjection of picrotoxin but not strychnine into CVPN.ConclusionsWe conclude that activation of GABAA receptors set the level of HR whereas AMPA to a greater extent than NMDA receptors elicit baroreflex changes in HR. Furthermore, activation of 5-HT1A receptors evokes bradycardia and enhances baroreflex changes in HR due to interactions with glycinergic neurons involving strychnine receptors. This study provides reference for future studies investigating how diseases alter neurochemical inputs to CVPN.

Effect of acute restraint stress on the tachycardiac and bradycardiac responses of the baroreflex in rats

In the present study, we evaluated cardiac baroreflex responses of rats submitted to acute restraint stress. The baroreflex was tested: immediately before, during a 30 min exposure to restraint stress, as well as 30 and 60 min after ending the stress session (recovery period). Restraint increased both mean arterial pressure (MAP) and heart rate (HR). The magnitude of tachycardiac responses evoked by intravenous infusion of sodium nitroprusside was higher during restraint stress, whereas that of bradycardiac responses evoked by intravenous infusion of phenylephrine was decreased. Restraint-evoked baroreflex changes were still observed at 30 min into the recovery period, although MAP and HR values had already returned to control values. The baroreflex was back to control values at 60 min of the recovery period. Intravenous administration of the selective β1-adrenoceptor antagonist atenolol blocked the restraint-evoked increase in the tachycardiac baroreflex response, but did not affect the effects on the bradycardiac response. In conclusion, the present results suggest that psychological stresses, such as those resulting from acute restraint, affect the baroreflex. Restraint facilitated the tachycardiac baroreflex response and reduced the bradycardiac response. Restraint-related effects on baroreflex persisted for at least 30 min after ending restraint, although MAP and HR had already returned to control levels. The cardiac baroreflex returned to control values 60 min after the end of restraint, indicating non-persistent effects of acute restraint on the baroreflex. Results also indicate that the influence of restraint stress on the baroreflex tachycardiac response is mainly dependent on cardiac sympathetic activity, whereas the action on the bradycardiac response is mediated by the cardiac parasympathetic component.

A new answer to an old question: does ageing modify baroreflex control of vascular sympathetic outflow in humans?

The baroreflexes are the primary neural mechanism by which arterial blood pressure (BP) is regulated on a beat-by-beat basis. Over 100 years of research has provided great insight into the structure and function of the baroreflexes in both health and disease (Eckberg & Sleight, 1992). In humans baroreflex function is commonly quantified by assessing changes in R–R interval or vascular sympathetic outflow during dynamic increases and/or decreases in BP. With advancing age, it is well accepted that baroreflex modulation of R–R interval is depressed (Monahan, 2007). In contrast, although less thoroughly studied, baroreflex control of vascular sympathetic outflow is generally believed to be unchanged with advancing age (Monahan, 2007). In this issue of The Journal of Physiology,Studinger et al. (2009) provide a new answer to an old question: does ageing alter baroreflex control of vascular sympathetic outflow in humans? Based upon their new data (Studinger et al. 2009), the simple answer to this question appears to be ‘yes’. However, whether ageing impairs or augments baroreflex control of vascular sympathetic outflow critically depends on whether the baroreflexes are responding to increases or decreases in BP. Specifically, the authors observed impaired sympathetic activation during BP falls and augmented sympathetic inhibition during BP increases. The ability to identify these divergent effects of ageing on baroreflex control of vascular sympathetic outflow was dependent on the authors' careful consideration and analysis of the data. The viewpoint that hysteresis is not present in the sympathetic arm of the baroreflex (Rudas et al. 1999) was challenged (Studinger et al. 2009). This analysis revealed that hysteresis was indeed present in the sympathetic arm of the baroreflex in both young and older adults (Studinger et al. 2009). The presence of hysteresis necessitated that data obtained during periods in which BP was increasing and decreasing be separately considered and analysed and not combined (‘pooled’) into a single analysis as previously recommended (Rudas et al. 1999). To provide insight into the site at which baroreflex changes occurred with ageing, carotid arterial imaging was performed during assessments of baroreflex function (Hunt et al. 2001). This allows the ‘integrated’ baroreflex response (vascular sympathetic outflow–BP relation) to be broken into its mechanical (carotid diameter–BP relation) and neural components (vascular sympathetic outflow–carotid diameter relation). These analyses revealed a smaller mechanical component of the baroreflex with ageing during both increases and decreases in BP (Studinger et al. 2009), consistent with the detrimental effect ageing exerts on large artery stiffness. Importantly, during increases in BP the neural component of the baroreflex was augmented to such a degree by age that it completely overcame the negative effects of ageing on the mechanical component of the baroreflex, resulting in increased integrated gain. In contrast, during decreases in BP, an enhanced neural component of the baroreflex was insufficient to overcome the effect of age on the mechanical component of the baroreflex, resulting in decreased integrated gain. Collectively, these data illustrate: (1) the importance that age-associated changes in large artery function exert on the sympathetic arm of the baroreflex, and (2) that the sympathetic arm of the baroreflex possesses an impressive level of neural plasticity with advancing age in humans. Of equal importance, similar age-associated changes in the sympathetic arm of the baroreflex occur in men and women and changes in baroreflex control of vascular sympathetic outflow were not influenced by habitual endurance exercise in older men (Studinger et al. 2009). The finding that baroreflex control of vascular sympathetic outflow is impaired with age in response to decreases, but not increases, in BP is interesting and may be of clinical importance. For instance, this finding may provide an explanation as to why hypotensive responses to certain vasodilator medications increase with age while the local vascular response remains unchanged (e.g. nitroprusside). By documenting hysteresis in the sympathetic arm of the baroreflex Studinger provides important new insight into the effect ageing, sex, and endurance-training status exert on baroreflex control of vascular sympathetic outflow in humans (Studinger et al. 2009). These findings should serve as a careful reminder to all investigators to adopt rigorous analysis techniques in future studies. Moreover, they may make us reflect on the validity of previous findings in which hysteresis in the sympathetic arm of the baroreflex may not have been fully considered and appreciated.

Cardiac autonomic function and baroreflex changes following 4 weeks of resistance versus aerobic training in individuals with pre‐hypertension

Cardiac autonomic modulation and baroreflex sensitivity (BRS) are altered in individuals with hypertension. Aerobic exercise (AE) training has been shown to improve both measures, yet little is known about the effects of resistance exercise (RE). The purpose of this study was to examine the heart rate variability (HRV) and BRS following 4 weeks of resistance or aerobic training in a population with borderline high blood pressure (BP). Twenty-nine mild hypertensives were recruited and randomly assigned to 4 weeks of RE or AE training. Before and after training, resting measures of HRV frequencies and BRS were obtained. There was a significant decrease in resting systolic BP for both exercise training modes (RE 136 +/- 3.0 pre- to 132 +/- 3.4 post-training vs. AE 142 +/- 4.0 pre- to 137 +/- 3.6 mmHg post-training, P = 0.019). Diastolic BP decreased significantly following both exercise training modes (RE 78 +/- 1.31 pre to 74 +/- 1.1 post vs. AE 80 +/- 1.7 pre to 77 +/- 1.6 mmHg post, P = 0.002). A significant time by training mode interaction for low frequency : high frequency (HF) ratio (P = 0.017) with AE decreasing the ratio (275.21 +/- 67.28 to 161.26 +/- 61.49) and RE increasing this ratio (143.73 +/- 65.00 to 227.83 +/- 59.41). Natural log-transformed (ln) HRV values showed a time-by-training mode interaction for ln HF (P = 0.05) as ln HF increased (4.7 +/- 0.38 to 5.4 +/- 0.35 ms(2)) following AE and decreased (5.98 +/- 0.37 to 5.76 +/- 0.42 ms(2)) following RE. BRS increased following aerobic training and decreased after resistance training (6.74 +/- 1.2 to 7.94 +/- 1.3 and 10.44 +/- 1.2 to 9.1 +/- 1.2 ms mmHg(-1) respectively, P = 0.021). Aerobic exercise improved the autonomic nervous system (increasing vagal tone, reducing sympathovagal balance while increasing BRS) while RE showed no improvements in cardiac autonomic tone and decreased BRS.