Diminished Baroreflex Sensitivity Research Articles

Cardiac-Gated Neuromodulation Increased Baroreflex Sensitivity and Reduced Pain Sensitivity in Female Fibromyalgia Patients.

The study presents a novel approach of programing pain inhibition in chronic pain patients based on the hypothesis that pain perception is modulated by dysfunctional dorsal medial nucleus tractus solitarii (dmNTS) reflex arcs that produce diminished baroreflex sensitivity (BRS) resulting from a conditioned response. This study tested whether administration of noxious and non-noxious electrical stimuli synchronized with the cardiac cycle resets BRS, reestablishing pain inhibition. A total of 30 pain-free normotensives controls (NC) and 32 normotensives fibromyalgia (FM) patients received two, ≈8 min-epochs of cardiac-gated, peripheral electrical stimuli. Non-painful and painful electrical stimuli were synchronized to the cardiac cycle as the neuromodulation experimental protocol (EP) with two control conditions (CC1, CC2). BRS, heart-rate-variability (HRV), pain threshold and tolerance, and clinical pain intensity were assessed. Reduced BRS in FM at baseline increased by 41% during two, ≈8 min-epochs of stimulation. Thresholds in FM increased significantly during the experimental protocol (all Ps < 0.001) as did HRV. FM levels of clinical pain significantly decreased by 35.52% during the experimental protocol but not during control stimulations (p < 0.001). Baroreceptor training may reduce FM pain by BRS-mediated effects on intrinsic pain regulatory systems and autonomic responses.

Effect of aging on cardiovascular responses to cold stress in humans

Abstract Cold exposure increases the risk of adverse events related to cardiovascular causes, especially in the elderly. In this review, we focus on recent findings concerning the impact of aging on the regulatory mechanisms of cold-induced cardiovascular responses. In response to cold exposure, the initial physiological thermoregulation in healthy young persons, such as cutaneous vasoconstriction to reduce heat loss, is attenuated in older individuals, resulting in a reduced ability of the older persons to maintain body temperature in cold environment. Impaired sympathetic skin response, reduced noradrenergic neurotransmitter synthesis, insufficient noradrenergic transmitters, and altered downstream signaling pathways inside the vascular smooth muscle may be among the underlying mechanisms for the maladaptive vasoconstrictive response to cold stress in the elderly. The increase in blood pressure during cold exposure in young persons may be further augmented in aging adults, due to greater central arterial stiffness or diminished baroreflex sensitivity with aging. Cold stress raises myocardial oxygen demand caused by increased afterload in both young and old adults. The elderly cannot adjust to meet the increased oxygen demand due to reduced left ventricular compliance and coronary blood flow with advancing age, rendering the elderly more susceptible to hypothermia-induced cardiovascular complications from cold-related diseases. These age-associated thermoregulatory impairments may further worsen patients' health risk with existing cardiovascular diseases such as hypertension, coronary artery disease, and heart failure. We searched PubMed for papers related to cold stress and its relationship with aging, and selected the most relevant publications for discussion.

Coexistence of fibromyalgia syndrome and inflammatory rheumatic diseases, and autonomic cardiovascular system involvement in fibromyalgia syndrome.

The spectrum of symptoms represented by fibromyalgia syndrome (FMS) has a profound effect on daily activities and impairs the quality of life. A considerable proportion of patients with inflammatory rheumatic diseases (IRDs) fulfill the FMS criteria, which can complicate the diagnosis, treatment, and follow-ups of IRD. In addition, the coexistence of FMS may cause unnecessary laboratory and radiological assessments. Several mechanisms have been proposed that may have a role in the etiopathogenesis of FMS, one of which is autonomic dysregulation. In studies evaluating cardiac autonomic dysfunction based on heart rate variability (HRV), there has been found to be a decrease in HRV and dominance of the sympathetic nervous system. Autonomic reactivity reflects modulations of several functions to overcome the existing state and conditions. Blunted autonomic reactivity has been found in some FMS patients, which makes it difficult for these patients to respond appropriately to unexpected stress sources that occur during daily living activities. Baroreceptor signals have an inhibitory influence on the central nervous system, and these impulses cause pain suppression. From this perspective, there are studies that have suggested the involvement of diminished baroreflex sensitivity in the etiology of FMS. The risk of endothelial dysfunction and increased arterial stiffness have been shown to occur in FMS patients due to autonomic dysfunction, sympathetic nervous system dominance, chronic stress, and pain. There is also evidence linking FMS with the risk of atrial and ventricular arrhythmias. Considering all these cardiovascular autonomic dysfunctions, tests that can confirm abnormalities should be performed when suspicion arises. There is a need for specific pharmacological and non-pharmacological treatment alternatives to be identified for subgroups of patients with cardiovascular system abnormalities. Key points • The frequency of FMS accompanying inflammatory rheumatic diseases is considerable and this coexistence leads to troubles in evaluating treatment response and determining appropriate medical treatment options in inflammatory rheumatic diseases. • Various cardiovascular autonomic abnormalities have been described in FMS patients. Among these, the most emphasized are autonomic dysfunction, the disruption of the balance between the sympathetic-parasympathetic nervous systems, blunted autonomic reactivity to acute stress, changes in baroreflex sensitivity, increased arterial stiffness, and electrophysiological alterations. • Autonomic cardiovascular dysfunction may be involved in the complex etiopathogenesis of the fibromyalgia syndrome and may trigger at least some symptoms.

Influence of brain-derived neurotrophic factor-tyrosine receptor kinase B signalling in the nucleus tractus solitarius on baroreflex sensitivity in rats with chronic heart failure.

Impairment of baroreflex function is associated with the progression of chronic heart failure (CHF) and a poor prognosis. The baroreflex desensitization in CHF is at least partly the result of central neuronal network dysfunction. The dorsal medial nucleus tractus solitarius (dmNTS) has long been appreciated as a primary site of baroreceptor afferent termination in the central nervous system. However, the influence of neurotransmitters and neuromodulators in the dmNTS on baroreflex function both in normal and CHF states is not fully understood. The present study provides the first evidence showing a tonic sympatho-inhibitory role for brain-derived neurotrophic factor (BDNF) neurotransmission in the dmNTS. Most importantly, BDNF- tyrosine receptor kinase B (TrkB) signalling in the dmNTS is integral for normal baroreflex function as indicated by the blunting of baroreflex sensitivity (BRS) following the antagonization of TrkB, which inhibited baroreflex gain and range. Furthermore, we found that the tonic sympatho-inhibition of BDNF was withdrawn in the CHF state, thus contributing to the increased sympathetic tone associated with CHF. Consistent with this finding, BDNF/TrkB antagonism had little effect on reducing BRS in CHF animals, which is corroborated by the observation of decreased TrkB expression in the dmNTS during CHF. Taken together, these results implicate a reduction in BDNF-TrkB signalling in the dmNTS during CHF that contributes to sympatho-excitation and baroreflex desensitization. The observation that the BDNF/TrkB pathway is impaired in the dmNTS during CHF provides a novel mechanism for understanding the central alterations that contribute to baroreflex desensitization during CHF. Chronic heart failure (CHF) results in blunting of arterial baroreflex sensitivity (BRS), which arises from alterations to both peripheral baroreceptors and central autonomic nuclei such as the nucleus tractus solitarius (NTS). Although glutamate is known to be an important neurotransmitter released from baroreceptor afferent synapses in the NTS, the influence of other neurotransmitters and neuromodulators remains unclear. Alterations to NTS signalling in CHF remain particularly undefined. The present study aimed to evaluate the role of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) receptor signalling in the NTS on baroreflex control both in healthy and CHF rats. To this end, we microinjected BDNF or the highly selective TrkB receptor antagonist [N2-2-2-oxoazepan-3-yl amino] carbonyl phenyl benzo (b)thiophene-2-carboxamide (ANA-12) into the dorsal medial NTS (dmNTS) of male Sprague-Dawley rats with coronary artery ligation-induced CHF and sham operated controls and recorded blood pressure and renal sympathetic nerve activity responses. We subsequently measured BRS before and after bilateral dmNTS microinjections of ANA-12. In sham rats, BDNF evoked a dose-dependent depressor and sympatho-inhibitory effect and ANA-12 produced the opposite response. Both of these responses were significantly blunted in CHF rats. Furthermore, bilateral microinjection of ANA-12 into the dmNTS greatly diminished baroreflex sensitivity in sham rats, whereas it had less of an effect in CHF rats. We observed decreased levels of TrkB protein and mRNA in the dmNTS of CHF rats. These data indicate that endogenous BDNF signalling in the NTS is integral for the maintenance of BRS and that BDNF/TrkB signalling is impaired in the NTS in the CHF state.

Chronic baroreflex activation effects on sympathetic nerve traffic, baroreflex function, and cardiac haemodynamics in heart failure: a proof‐of‐concept study

AimsHeart failure (HF) pathophysiology is believed to be mediated by autonomic dysfunction, including chronic sympathoexcitation and diminished baroreflex sensitivity, which correlate with mortality risk. Baroreflex activation therapy (BAT) is a device-based treatment providing chronic baroreflex activation through electrical stimulation of the carotid sinus. BAT chronically reduces sympathetic activity in resistant hypertension. The purpose of this investigation is to determine BAT effects in clinical HF.Methods and resultsIn a single-centre, open-label evaluation, patients with NYHA class III HF, EF <40%, optimized medical therapy, and ineligible for cardiac resynchronization received BAT for 6 months. Efficacy was assessed with serial measurement of muscle sympathetic nerve activity (MSNA) and clinical measures of quality of life and functional capacity. Eleven patients participated in the trial. MSNA was reduced over 6 months from 45.1 ± 7.7 to 31.3 ± 8.3 bursts/min and from 67.6 ± 12.7 to 45.1 ± 11.6 bursts/100 heartbeats, decreases of 31% and 33%, respectively (P < 0.01). Concomitant improvements occurred in baroreflex sensitivity, EF, NYHA class, quality of life and 6 min hall walk (6MHW) distance (P ≤ 0.05 each). On an observational basis, hospitalization and emergency department visits for worsening HF were markedly reduced. One complication, perioperative anaemia requiring transfusion, occurred during the study.ConclusionBAT was safe and provided chronic improvement in MSNA and clinical variables. Based on present understanding of HF pathophysiology, these results suggest that BAT may improve outcome in HF by modulating autonomic balance. Prospective, randomized trials to test the hypothesis are warranted.

Diurnal Variation in the Mechanical and Neural Components of the Baroreflex

Diminished baroreflex sensitivity in the morning negatively influences morning coronary blood flow and blood pressure control in hypertensive patients. Our aim was to determine the contribution of the mechanical and neural components of the cardiac baroreflex to diurnal variation in blood pressure control. In 12 healthy participants, we used the modified Oxford method to quantify baroreflex sensitivity for rising (G(up)) and falling (G(down)) pressures in the morning (7:00 am) and afternoon (4:00 pm). Beat-to-beat blood pressure, R-R intervals, and carotid artery diameter measurements were recorded. Integrated sensitivity was determined by plotting R-R intervals against systolic blood pressure. The mechanical component was carotid artery diameter plotted against systolic blood pressure, and the neural component was R-R intervals plotted against carotid artery diameter. Linear mixed models were used to compare the integrated, mechanical, and neural sensitivities between morning and afternoon. We found significant diurnal variation in integrated sensitivity, with an attenuated response in the morning (G(up)=13.0±0.6; G(down)=6.3±0.4 ms/mm Hg) when compared with the afternoon (G(up)=15.1±0.6; G(down)=12.6±0.4 ms/mm Hg). For rising pressures, the diminished integrated sensitivity in the morning was caused by a reduction in mechanical sensitivity, whereas for falling pressures it was caused by a reduction in neural sensitivity. Our findings explicate the mechanisms underlying diurnal variation in baroreflex function. Pharmacological and lifestyle interventions targeted specifically at the diminished component of the cardiac baroreflex in the morning may lead to better management of hypertension.

Acute superoxide scavenging restores depressed baroreflex sensitivity in renovascular hypertensive rats

In some pathological conditions such as hypertension, there is an impairment in the autonomic control of blood pressure resulting in changes in baroreflex sensitivity. In the present study we tested the hypothesis that acute superoxide scavenging would restore the reduced baroreflex sensitivity in renovascular hypertension. Male Wistar rats underwent 2-Kidney-1-Clip (2K1C) or sham surgery and were maintained untouched for six weeks to develop hypertension. After six weeks, animals from the 2K1C group were hypertensive when compared to the sham group (165 ± 9 vs. 108 ± 7 mmHg, P < 0.05). As a proof of principle for the hypertension model adopted, animals from the 2K1C group presented increased non-clipped kidney and cardiac mass index and reduced clipped kidney mass index. Regarding baroreflex, 2K1C rats presented diminished baroreflex sensitivity when compared to the sham group (2K1C + saline: −1.61 ± 0.15 vs. sham + saline: −2.79 ± 0.24 bpm mm Hg −1, p < 0.05). Moreover, acute administration of Vitamin C (150 mg/Kg, i.v.) restored baroreflex sensitivity in 2K1C rats (2K1C + Vit C: −3.08 ± 0.37 vs. 2K1C + saline: −1.61 ± 0.15 bpm mm Hg −1, p < 0.05). Furthermore, administration of apocynin (30 μg/Kg, i.v.), a NADPH oxidase inhibitor, also improved baroreflex sensitivity in the 2K1C group (2K1C + apocynin: −2.81 ± 0.24 vs. 2K1C + saline: −1.61 ± 0.15 bpm mm Hg −1, p < 0.05). In addition, autonomic blockade with either methylatropine or propranolol reduced the changes in heart rate to the same extent in all groups suggesting that improved baroreflex sensitivity by antioxidants were mediated by improvement in autonomic function. Taken together, these data suggest that NADPH oxidase-derived reactive oxygen species are involved in the blunted baroreflex sensitivity in renovascular hypertension and that acute scavenging of superoxide restores baroreflex sensitivity.

Predictability of baroreflex sensitivity induced by phenylephrine injection via frequency domain indices computed from heart rate and systolic blood pressure signals during deep breathing

Diminished baroreflex sensitivity (BRS) is related to increased risk of sudden cardiac death in myocardial infarction patients and can be used as an indicator for risk level. The BRS is traditionally estimated invasively using vasoactive drugs, such as phenylephrine injection. This method has been widely accepted as a standard in clinical research. Due to its clinical importance, alternative BRS assessment methods have been investigated over the years to eliminate the use of drugs. In this study, the BRS obtained by drug-based (pharmacological) assessment was predicted from a subset of non-pharmacological indices computed from heart rate and systolic pressure signals. In the first phase of a two-phase experimental paradigm, 16 subjects were asked to perform two deep breathings with a 2-min delay in between. In the second phase, the BRS was measured by phenylephrine injection. Indices computed from the first phase describing the spectral and time domain properties of the heart rate and systolic pressure signals were used as predictors to estimate the pharmacological BRS of each subject. In addition to individual spectrum of beat-to-beat interval and systolic blood pressure, indices from cross-spectrum were also computed and evaluated as predictors. A leave one out method was employed to estimate the generalization capacity of the system and explore subset of indices, which gives the highest correlation between pharmacological and predicted BRS. Two predictors provided the highest correlation ( r = 0.87, p = 1.16 × 10 −5) with pharmacological BRS. The algorithm selected consistently normalized cross-power about the Mayer frequency and average magnitude square coherence in the high frequency band as predictors. These results indicate that the pharmacological BRS can be estimated from the combination of non-pharmacological spectral indices computed from beat-to-beat interval and systolic blood pressure signals obtained during deep breathing and therefore may eliminate the use of drugs.

Global Disturbances in Autonomic Function Yield Cardiovascular Instability and Hypertension in the Chromogranin A Null Mouse

We reported previously that chromogranin A (Chga) knockout (KO) mice are hypertensive and hyperadrenergic. Here we sought to determine the basis of such alterations by probing physiological, biochemical, and pharmacological responses to perturbations of the autonomic nervous system. In the conscious state, KO mice had substantially elevated basal high blood pressure (BP) and heart rate (HR); immobilization stress caused increments in systolic BP and HR in both wild-type (WT) and KO mice, with higher maxima but blunted increments in the KO state. Catestatin (CST; CHGA(352-372)) selectively diminished stress-induced increments in BP and HR in KO mice, implicating CST as an antihypertensive peptide, even in stressful conditions. Heightened plasma catecholamines in KO mice returned to WT level after CST. Stress caused further increments in catecholamines in WT mice but no change in KO mice. KO mice displayed diminished baroreflex sensitivity in response to either phenylephrine or sodium nitroprusside, accounting for exaggerated pressor and depressor responses to these compounds; baroreceptor function was normalized by CST. To probe the relative roles of endogenous/basal sympathetic vs. parasympathetic tone in control of BP and HR, we used the muscarinic-cholinergic antagonist atropine or the beta-adrenergic antagonist propranolol; HR and BP responses to each antagonist were exaggerated in KO animals. We conclude that ablation of Chga expression results in global disturbances in autonomic function, both sympathetic and parasympathetic, that can be abrogated (or rescued), at least in part, by replacement of CST. The results point to mechanisms whereby CHGA and its CST fragment act to control cardiovascular homeostasis.

New insights into orthostatic hypotension

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(690): Parental history of chronic pain predicts diminished baroreflex sensitivity: Implications for hypertension risk

Chronic pain (CP) has been associated with reduced baroreflex sensitivity (BRS) that may impact on both cardiovascular and pain regulatory processes. Hypertension (HTN) is also associated with reduced BRS, and research suggests CP is associated with increased HTN prevalence. Whether interrelationships between CP, BRS, and HTN risk reflect an underlying potentially heritable factor has not been studied. We therefore tested whether parental history of CP (PHCP) and HTN (PHHTN), which are associated with increased CP and HTN risk respectively, were associated with altered BRS. Simultaneous beat-to-beat blood pressure and electrocardiogram data were obtained during seated rest in 22 healthy controls and 17 CP subjects in two separate sessions. Mean spontaneous resting BRS in the time domain was derived from these measures using the sequence method (sequence up and down). PHCP+ subjects were marginally more likely to have CP themselves (p<.07). Across subject types, PHCP+ subjects had lower BRSup than PHCP- subjects (p<.001). General linear model analyses revealed significant Type X PHCP and Type X PHHTN interactions on BRSup (p’s<.05). PHCP+ controls had moderately lower BRS than PHCP- controls; CP subjects with PHCP- status had exaggerated BRS relative to controls, whereas CP subjects with PHCP+ status had notably lower BRS values than any other group. PHHTN+ status was associated with decreased BRS in controls, but increased BRS in CP subjects. BRSdown analyses revealed a significant PHCP X PHHTN interaction (p<.05). This was due primarily to substantially higher BRS in subjects negative for both PHCP and PHHTN. Results suggest that PHCP+ status combined with presence of CP is particularly detrimental to baroreflex function, with possible implications for increased hypertension risk. Individuals with a negative parental history for both CP and HTN display more effective cardiovascular modulation, which may be associated with diminished hypertension risk. Chronic pain (CP) has been associated with reduced baroreflex sensitivity (BRS) that may impact on both cardiovascular and pain regulatory processes. Hypertension (HTN) is also associated with reduced BRS, and research suggests CP is associated with increased HTN prevalence. Whether interrelationships between CP, BRS, and HTN risk reflect an underlying potentially heritable factor has not been studied. We therefore tested whether parental history of CP (PHCP) and HTN (PHHTN), which are associated with increased CP and HTN risk respectively, were associated with altered BRS. Simultaneous beat-to-beat blood pressure and electrocardiogram data were obtained during seated rest in 22 healthy controls and 17 CP subjects in two separate sessions. Mean spontaneous resting BRS in the time domain was derived from these measures using the sequence method (sequence up and down). PHCP+ subjects were marginally more likely to have CP themselves (p<.07). Across subject types, PHCP+ subjects had lower BRSup than PHCP- subjects (p<.001). General linear model analyses revealed significant Type X PHCP and Type X PHHTN interactions on BRSup (p’s<.05). PHCP+ controls had moderately lower BRS than PHCP- controls; CP subjects with PHCP- status had exaggerated BRS relative to controls, whereas CP subjects with PHCP+ status had notably lower BRS values than any other group. PHHTN+ status was associated with decreased BRS in controls, but increased BRS in CP subjects. BRSdown analyses revealed a significant PHCP X PHHTN interaction (p<.05). This was due primarily to substantially higher BRS in subjects negative for both PHCP and PHHTN. Results suggest that PHCP+ status combined with presence of CP is particularly detrimental to baroreflex function, with possible implications for increased hypertension risk. Individuals with a negative parental history for both CP and HTN display more effective cardiovascular modulation, which may be associated with diminished hypertension risk.

Parasympathetic-mediated atrial fibrillation during tilt test associated with increased baroreflex sensitivity

The autonomic mechanism that triggered atrial fibrillation in a patient during tilt test was investigated. Neurocardiogenic syncope is often characterized by diminished baroreflex sensitivity during the hypotension period. Increased barorereflex sensitivity preceding the onset of atrial fibrillation in tilt testing may indicate the involvement of a vagally mediated mechanism, as shown in the present case.

Autonomic Dysfunctions in Patients with Anxiety Throughout Therapy

Abstract Patterns of autonomic cardiovascular regulation were studied in patients with anxiety throughout the course of an intensive inpatient rehabilitation therapy at rest, and in response to an anxiety provocation, in order to measure reactivity changes. Patients had to meet the ICD-10 criteria: F40.0 (agoraphobia), F40.00 (agoraphobia without panic attacks), F40.01 (agoraphobia with panic attacks), or F41 (panic disorder). Thirty-eight patients (13 males, 25 females) were examined after recruitment (T1) and at the end of treatment (T2). Each laboratory session consisted of a resting baseline (5min) and two stress tests of 8min (presentation of word pairs with either neutral or with anxiety-related content). A continuous assessment of ECG, blood pressure, breathing pattern, and thoracic impedance allowed the calculation of heart rate variability (power spectra), baroreflex sensitivity, stroke volume, vascular compliance, and total peripheral resistance. In general, therapy had little impact on the parameters of autonomic cardiovascular regulation, neither on resting level nor on reactivity. Diminished baroreflex sensitivity values in our patients with anxiety were observed; in particular, 15% of the patients had values below 3ms/mmHg, which indicates an increased risk for cardiovascular mortality. Low baroreflex sensitivity in this group goes along with further changes within the cardiovascular system (higher heart rate, diminished heart rate variability, lower stroke volume, higher vascular compliance). This general effect describes altered sympathetic/parasympathetic balance and may be the consequence of illness-related changes in behavior. Our results suggest that a careful cardiovascular examination of patients with anxiety will detect patients with clinically significant cardiovascular alterations. This might lead to a more complex intervention in these patients including, for example, exercise training.

Mendelian hypertension with brachydactyly as a molecular genetic lesson in regulatory physiology.

Mendelian forms of hypertension have delivered a treasure trove of novel genes. To date, the molecular mechanisms of five such syndromes have been largely clarified, including glucocorticoid-remediable aldosteronism, Liddle's syndrome, apparent mineralocorticoid excess, an activating mutation of the mineralocorticoid receptor, and pseudohypoaldosteronism type 2. Each of these conditions features salt sensitivity with increased sodium and volume reabsorption by the kidney and low plasma renin activity. None of the gene loci for these syndromes has been convincingly linked to hypertension in the general population. We are investigating kindreds who have autosomal-dominant hypertension and brachydactyly. Affected persons invariably have both anomalies. The hypertension is severe and results in death at about age 50 years from stroke. The condition resembles essential hypertension, because renin, aldosterone, and norepinephrine responses are normal and no salt sensitivity is present. The response to antihypertensive drugs is general. Another feature is diminished baroreflex sensitivity with markedly impaired blood pressure buffering. Furthermore, the ventrolateral medulla may be compromised in these patients, because neurovascular anomalies are a regular finding. We mapped the gene(s) for this disease to chromosome 12p and narrowed the chromosomal region by studying more affected families. Interestingly, the same locus was recently mapped in Chinese families with essential hypertension. Our 3-centimorgan region contains genes encoding a phosphodiesterase, an ATP-dependent potassium channel, and its regulator the sulfonylurea receptor 2. Screening of the coding regions revealed that none of these candidate genes harbor obvious mutations; however, other genetic mechanisms may nevertheless compromise their function. Our study underscores the importance of regulatory physiology to the understanding of a complex genetic syndrome.

Effect of systolic blood pressure and carotid stiffness on baroreflex gain in elderly subjects.

Aging is associated with diminished baroreflex sensitivity (gain), which predisposes elderly people to orthostatic hypotension, syncope, and cardiovascular morbidity. Aging is also associated with systolic blood pressure (SBP) elevation and carotid artery stiffness, which may both affect baroreflex gain. We examined the relation between SBP, carotid artery stiffness, and baroreflex gain in 34 healthy elderly (71 +/- 4 years) and 10 healthy young (31 +/- 3 years) subjects. SBP (Finapres) and carotid artery stiffness (ultrasound measures of relative carotid artery diameter changes during each blood pressure pulse) were measured. The gain of the transfer function relating the R-R interval to SBP fluctuations at a frequency of 0.05-0.15 Hz was used to assess cardiovagal baroreflex gain. Elderly subjects had higher carotid artery stiffness (14.2 +/- 5.1 vs 6.6 +/- 1.8, p <.05), higher SBP (146 +/- 24 vs 125 +/- 8 mmHg, p =.012), and lower baroreflex gain (8.2 +/- 6.4 vs 16.3 +/- 7.4, p <.05) than young subjects. Among all subjects, SBP and carotid artery stiffness both correlated with baroreflex gain (r = -.39, p =.02 for both). Although SBP was related to stiffness across all subjects, this relation was not present among the elderly subjects. Within the elderly group, only SBP was independently related to baroreflex gain (R(2) =.51, p =.009). SBP elevation in elderly people may affect the neural or cardiac response to blood pressure fluctuations, independent of the mechanical properties of barosensory regions in the carotid artery. Future studies should examine the effect of pharmacologic treatment of hypertension on baroreflex gain in elderly people.

Geomagnetic Field Decreases Cardiovascular Variability

The objective was to study the influence of geomagnetic activity as reflected by K- and Ak-indices on mean arterial blood pressure (MAP), heart rate (HR), and hemodynamic index (HDI, HR.MAP), and on cardiovascular variability expressed by MAP and HR standard deviation (SD). Baroreceptor function was assessed from measurement of the rate-pressure response (ΔHR/ ΔMAP) for intravenous phenylephrine. One hundred forty-three experimental runs were canied out in 29 rabbits. Rabbits were sedated by pentobarbital infusion (5 mg/kg/h) during 50-min experiments. MAP, HR, HDI, MAP SD, and HR SD were measured after a 10-min resting period for 5 min, followed by ΔHR/ΔMAP testing. We found a significant positive correlation of geomagnetic activity with MAP and HDI, and a negative correlation with ΔHR/ΔAP, MAP SD, and HR SD. Diminished baroreflex sensitivity and sympathetic hyperactivity may participate in the observed effects, and explain the greater incidence of severe cardiovascular events during magnetic storms.

SYMPATHETIC ACTIVITY AND PRESYNAPTIC ADRENOCEPTOR FUNCTION IN PATIENTS WITH LONGSTANDING ESSENTIAL HYPERTENSION

To assess the contribution of the sympathetic nervous system to the hypertension in patients with longstanding essential hypertension. Overall sympathetic function, presynaptic adrenoceptors and neuronal re-uptake were examined after withdrawal of medication for at least 3 weeks in eight patients with longstanding essential hypertension and in eight carefully matched normotensive control subjects. Minimal forearm vascular resistance after 10 min ischaemia was used as a measure of structural vascular changes. Overall sympathetic tone was assessed using tilt testing and pressor dose infusion of noradrenaline. The presence and function of presynaptic adrenoceptors and the neuronal re-uptake of noradrenaline were evaluated in the forearm using tracer noradrenaline kinetics with measurement of forearm noradrenaline plasma appearance rate and noradrenaline plasma spillover. Intra-arterial infusions of tritiated noradrenaline, the endogenous alpha- and beta-adrenoceptor agonist adrenaline, the alpha-adrenoceptor blocker phentolamine, the non-adrenergic vasodilator sodium nitroprusside and the neuronal re-uptake inhibitor desipramine were given in the forearm. We found that the hypertensives had higher minimal forearm vascular resistance, indicating structural vascular changes; decreased overall sympathetic activity, indicated by a lower basal whole-body noradrenaline production rate; enhanced vasopressor sensitivity for exogenously administered noradrenaline with decreased arterial baroreflex sensitivity; indications of decreased forearm neuronal re-uptake; evidence consistent with the presence of presynaptic, release-facilitating beta-adrenoceptors in the forearm, apparently not functionally different between the two groups; and undecisive evidence for the presence of functional presynaptic alpha-adrenoceptors in the forearm. In patients with longstanding essential hypertension we found decreased overall sympathetic activity, with indications of decreased forearm neuronal re-uptake, which might have a compensatory role. We found indications of structural vascular changes and diminished baroreflex sensitivity in the hypertensives, which contribute to the hypertension. However, peripheral presynaptic, release-facilitating beta-adrenoceptors seem to be present, which are functionally not clearly different between the two groups. Observations on peripheral presynaptic alpha-adrenoceptors were inconclusive.

Baroreflex sensitivity and pressor responses in a rat model of uraemia.

Baroreflex sensitivity and pressor responsiveness to exogenous noradrenaline, angiotensin II and arginine vasopressin were determined in a rat model of uraemia. The slope of the regression line relating delta heart rate to delta blood pressure after phenylephrine administration was significantly less in the renal failure group than the normal control group, indicating a reduction of baroreflex sensitivity in the setting of uraemia. The pressor response to noradrenaline and angiotensin II was significantly less in the renal failure group whereas there was no difference in delta blood pressure on administration of arginine vasopressin. It is concluded that diminished baroreflex sensitivity does not contribute to the pathogenesis of hypertension in uraemia by the hypothesized mechanism of allowing the pressor effect of endogenous pressor substances to go unbuffered.

BAROREFLEX EFFECTS OF ALTHESIN INFUSIONS TO SUPPLEMENT NITROUS OXIDE ANAESTHESIA IN MAN

The effects on baroreflex control of heart rate, of two infusion rates of Althesin (18 and 36 micrograms kg-1 min-1 as total steroid) to supplement 66% nitrous oxide in oxygen anaesthesia, have been studied in six younger (mean age 35.5 yr) and six older (mean age 61.0 yr) patients. Steady-state anaesthesia at both infusion rates was associated with diminished baroreflex sensitivity and resetting of the reflex to allow lower arterial pressures to be maintained without tachycardia.

Diminished baroreflex sensitivity in high blood pressure.

Sudden intravenous injections of small amounts of angiotensin or phenylephrine were given to 30 subjects to produce modest, brief increases in directly measured systemic arterial pressure. A plot of each systolic pressure against the second succeeding cardiac cycle length produced a linear distribution, the slope of which was expressed as the millisecond increase in cycle length per mm Hg rise in systolic pressure. The slope is an index of baroreflex sensitivity and was found to have an average value of 12.8 in 18 subjects without hypertension and 2.8 in 12 others with hypertension. When all results were pooled, there was an inverse relationship between the resting mean arterial pressure and slope of the baroreflex regression lines. The findings demonstrate reduced sensitivity of the baroreflexes in hypertension, with respect to control of heart rate. A distinction is made between this change in sensitivity and simple resetting of the reflex.