Cardiovascular instability and baroreflex activity in a patient with tetanus

In a patient with tetanus we tested the hypothesis that the hyperadrenergic cardiovascular instability might be due to impairment of the baroreceptor reflex by the tetanus toxin. Baroreflex sensitivity assessed with the phenylephrine method was found to be normal. Changes in arterial pressure correlated inversely with relative changes in plasma volume but not with plasma catecholamine levels. There were both extreme hypo- and hyperadrenergic episodes. We conclude that sympathetic overactivity in tetauns temporarily overrules a functionally intact baroreflex leading to severe blood pressure instability with episodes of hypertension.     

The lateral septal area modulates the baroreflex in unanesthetized rats

The septal lateral area (LSA) is a limbic structure that is involved with autonomic and behavioral responses. In the present study we report the effect of acute and reversible LSA synaptic inhibition on the parasympathetic and the sympathetic components of baroreflex in unanesthetized rats. Neurotransmission was temporarily inhibited by bilateral microinjection of the nonselective synapse blocker CoCl(2) in the LSA. Bilateral microinjection of 100 nL of 1 mM CoCl(2) into the LSA did not affect blood pressure or heart rate baseline, suggesting no tonic LSA influence on resting cardiovascular parameters. However, 10 min after CoCl(2) microinjections, maximum tachycardiac responses to blood pressure decreases caused by intravenous infusion of sodium nitroprusside and bradycardiac responses evoked by blood pressure increases caused by intravenous infusion of phenylephrine were enhanced when compared with control values. These enhancement of both the tachycardiac and bradycardiac reflex evoked increase of baroreflex gain. Baroreflex activity returned to control values 60 min after CoCl(2) microinjections, confirming the reversible blockade. The present results indicate an involvement of the LSA in baroreflex modulation. Data suggest that synapses in the LSA play a tonic inhibitory influence on both the sympathetic and the parasympathetic components of the baroreflex in unanesthetized rats.     

Baroreflex mechanisms in major depression

BACKGROUND: Recent studies have shown that depressive disorder is associated with impaired baroreceptor or baroreflex sensitivity, which is proposed to be a predisposing factor for sudden death in patients with manifest cardiac disease. These studies have not evaluated the afferent and efferent components of the cardiac baroreflex loop or other baroreflex mechanisms that regulate target processes (cardiac metabolism and blood pressure variability) related to the impairment. The objective of this study was to gain more insight into autonomic functioning in depressive disorder to more fully examine the potential basis for increased cardiac mortality. METHODS: The subjects were 28 women and men with unipolar major depression who were taking antidepressant medications and who were in partial remission and free of cardiovascular or other serious disease, and 28 healthy control subjects matched for sex, age, and ethnicity. The two samples were compared for negative affective dispositions (anger expression, hostility, defensiveness, anxiety), spontaneous (closed-loop) baroreflex activity, heart rate, heart rate variability, systolic blood pressure, and heart rate-systolic blood pressure double product under resting conditions. RESULTS: Depressed patients showed a general disposition to anger suppression coupled with higher hostility and anxiety, and lower defensiveness. The patients showed higher general sympathetic activity (high levels of blood pressure, low-frequency heart rate variability) and lower parasympathetic-related activity (high heart rate and reduced high frequency heart rate variability) with affected cardiac metabolism estimated by the double product. Depressed patients had lower baroreflex sensitivity related to a higher gain of the afferent component of the baroreflex without respective gain adjustment of its efferent component (reflex gain 'de-afferentation'). It was coupled with a compensatory higher number of effective baroreflex reactions (reflex gating 're-afferentation'). Antidepressant agents and depressed mood had additional independent effects on baroreflex sensitivity through the efferent component of the cardiac baroreflex loop. CONCLUSIONS: The data indicate that different baroreflex components and mechanisms may be impaired in patients with depression and may contribute to their increased cardiac risk.     

Effects of ketamine and propofol on autonomic cardiovascular function in chronically instrumented rats

In this study C. we systematically examined the effects of ketamine and propofol at various doses (5-20 mg/kg) on blood pressure, heart rate and renal sympathetic nerve activity in chronically instrumented Wistar rats. We also assessed the effects of these anesthetics on the baroreflex control of heart rate and renal sympathetic nerve activity. Ketamine (10 mg/kg) increased blood pressure by 30.0+/-4.5%, heart rate by 17.7-3.3% and renal sympathetic nerve activity by 38.8+/-14.6%, while propofol (10 mg/kg) decreased blood pressure by 18.9+/-3.5%, heart rate by 5.5+/-2.5% and renal sympathetic nerve activity by 7.5+/-2.1%. These variables showed dose-dependent responses to both agents. Both ketamine and propofol decreased the range and maximum gain of the logistic function curve obtained by relating mean blood pressure to heart rate and blood pressure to renal sympathetic nerve activity. In conclusion, ketamine and propofol had different effects on autonomic cardiovascular function, but attenuated the baroreflex sensitivity of heart rate and renal sympathetic nerve activity in a dose-dependent manner. These results suggest the possibility that baroreflex sensitivity may reflect the depth of anethesia.     

Status epilepticus produces chronic alterations in cardiac sympathovagal balance

Purpose:   Status epilepticus (SE) activates the autonomic nervous system, increasing sympathetic nervous system control of cardiac function during seizure activity. However, lasting effects of SE on autonomic regulation of the heart, which may contribute to mortality following seizure activity, are unknown. Therefore, autonomic control of cardiac function was assessed following SE.
Methods:   Using Sprague-Dawley rats after 1–2 weeks of recovery from lithium-pilocarpine-induced SE or control procedures, we tested  overall sympathovagal control of the heart, the individual contributions of the sympathetic and parasympathetic components of the autonomic nervous system, and baroreflex sensitivity.
Results:   SE induced a chronic shift in sympathovagal balance toward sympathetic dominance resulting from decreased parasympathetic activity. Baroreflex sensitivity to increased blood pressure was also decreased, likely resulting from diminished vagal activation.
Discussion:   Chronic alterations in autonomic regulation of cardiac function, characterized by increased sympathetic dominance, occur following SE and likely contribute to subsequent increased cardiac risk and mortality.     

Autonomic nervous system activity in normotensive subjects with a family history of hypertension

Abstract This study was designed to address alterations in autonomic nervous system activity in normotensive subjects with a family history of hypertension. We compared the autonomic nervous system activity in 59 normotensives with a family history of hypertension and 46 normotensives with no family history of hypertension. Skin blood flow was measured using laser-Doppler method on the nailfold skin in the resting condition, during systemic cooling and during upright tilting. Finger blood pressure, pulse and ECG were monitored by a finapres device. Heart rate, systolic pressure and microvascular flow power spectral analyses were performed using fast Fourier transformation. Baroreflex sensitivity was estimated with the sequence method. Compared to the control group, normotensives with a family history of hypertension showed significantly higher systolic pressure, decreased proportion and area of the high-frequency band of the heart rate variability power spectrum and reduced baroreflex sensitivity in the resting condition as well as a decreased proportion and area of the high-frequency band of the heart rate variability power spectrum during systemic cooling. We also proved a different time course of baroreflex sensitivity during upright tilting in the two groups. In contrast, we did not find any significant differences in the parameters of systolic pressure and microvascular variability power spectra between the two groups. Our results indicate that even normotensives with a family history of hypertension exhibit an increased ratio of sympathetic to parasympathetic activity at the cardiac level; however, they do not show any alteration of the vascular sympathetic reactivity.     

Parasympathetic hyperresponsiveness and bradyarrhythmias during apnoea in hypertension

Voluntary end-expiratory apnoea in a 23-year-old asymptomatic mild hypertensive patient consistently elicited bradyarrhythmias (complete heart block and sinus pause) and sympathetic activation to muscle blood vessels, indicating simultaneous sympathetic and parasympathetic activation during apnoea. The sympathetic bradyarrhythmic response to apnoea was potentiated by hypoxia and eliminated by atropine. Baroreflex activation also attenuated the bradycardic response to apnoea.A 43-year-old hypertensive patient with sleep apnoea also exhibited bradyarrhythmias (sinus arrest for up to 10 s) and a fall in perfusion pressure to <50 mmHg during episodes of sleep apnoea. These cardiovascular changes were associated with a reduction in oxygen saturation to levels as low as 35%. Neither patient was on any medication.Simultaneous sympathetic and parasympathetic activation during episodes of apnoea may predispose to cardiovascular catastrophe. These chemoreflex mediated autonomic changes are inhibited by baroreflex activation. We propose that patients with impaired baroreflexes (patients with hypertension or heart failure and premature infants) may be especially susceptible to excessive autonomic responses to chemoreflex stimulation during periods of apnoea. In these patient groups, brady-arrhythmias, hypoxia, hypoperfusion and sympathetic activation during apnoea may predispose to sudden death.     

Adrenergic and vagal baroreflex sensitivity in autonomic failure

BACKGROUND: The baroreflex is responsible for maintaining a stable blood pressure (BP) despite changes in body positions and fails in many autonomic disorders. The baroreflex regulates BP by changing the heart rate (vagal component) and total peripheral resistance (adrenergic component). Baroreflex sensitivity is widely used to quantify the vagal component of the reflex, but the adrenergic component is not quantifiable in the autonomic laboratory. OBJECTIVES: To develop and validate an index of adrenergic baroreflex sensitivity. DESIGN: We validated this index with microneurographically recorded muscle sympathetic nerve discharges generated by the Valsalva maneuver and verified it against groups of patients with graded severities of adrenergic failure. RESULTS: Adrenergic baroreflex sensitivity relates BP recovery time to the preceding decrease in BP evoked by the Valsalva maneuver. This index showed a graded and highly significant impairment in 3 groups of patients, (1) those with orthostatic hypotension (n = 26), (2) those with borderline orthostatic hypotension (n = 34), and (3) those with impaired reflex vasoconstriction without orthostatic BP change (n = 24), when compared with an age- and sex-matched control group (n = 29). Adrenergic baroreflex sensitivity better tracked the severity of adrenergic failure than the vagal component of baroreflex sensitivity and provides a much needed index to quantify total peripheral resistance changes in patients with adrenergic failure. CONCLUSIONS: The 2 indices of baroreflex sensitivity separately evaluate the vagal and adrenergic components of the baroreflex. Combined, they provide an index of composite or global baroreflex function.     

Vagal and sympathetic heart rate and blood pressure control in adult onset <Emphasis Type="Italic">PHOX2B</Emphasis> mutation–confirmed congenital central hypoventilation syndrome

Background Children with Congenital Central Hypoventilation Syndrome (CCHS) typically present as newborns with alveolar hypoventilation. With the advent of genetic testing, parents of affected children and other unrelated adults, all heterozygous for the disease-defining PHOX2B polyalanine expansion mutation with the 20/25 genotype, are being identified in adulthood. Though children with PHOX2B mutation-confirmed CCHS demonstrate ANS dysregulation, including altered heart rate and blood pressure control, it is unknown if adults with CCHS have similarly affected autonomic function in blood pressure control. Methods and Results An autonomic profile of blood pressure control has been studied with recording of muscle sympathetic activity and spectral analysis of heart rate and blood pressure variability of one adult patient with alveolar hypoventilation and the 20/25 PHOX2B genotype. All parameters of heart rate variability were reduced. Cardiac baroreflex sensitivity was decreased. Sympathetic responses to Valsalva maneuver, hypoxemia, isometric exercise and cold pressor were blunted. Conclusion In summary, we found a reduced cardiac baroreflex and a blunted sympathetic mediated response in the individual with adult-onset CCHS, possibly due to dysfunction in the afferent pathway. Our results confirm that PHOX2B affects the development of the autonomic nervous system, possibly causing absence of normal maturation of carotid body and visceral sensory ganglia and leading to autonomic dysfunction in adult-onset CCHS.     

The cold face test: A non-baroreflex mediated test of cardiac vagal function

Application of cold to the face evokes potent bradycardia and a pressor response, similar to the diving reflex. However, the role of the baroreceptors in this response is unclear. Ten healthy controls and two patients with baroreflex impairment were recruited. A cold face test (CFT) was induced by the application of three cold packs (0.5°C) to the face. Heart rate (ECG), blood pressure (Finapres) and skin temperature (forehead electrode) were recorded continuously. All data were analyzed using unpaired Students t-tests, and expressed as mean ± SD. In all controls, CFT induced bradycardia. The mean onset latency was 5.6 ± 4.6 s, and the maximal bradycardia was seen at 35.8 ± 15.8 s. Systolic blood pressure increased in eight controls, with a mean onset latency of 18.8 ± 16.6 s and a peak rise at 38.7 ± 22.7 s. In the controls, bradycardia preceded the pressor response. The heart rate and blood pressure changes during CFT had a longer latency than baroreflex evoked responses. Moreover, one subject had bradycardia despite a fall in blood pressure. The two patients had abnormal Valsalva ratios and no change in heart rate during tilt, indicating impairment of the baroreflex. However, both their heart rate and blood pressure responses to CFT were normal. These data are further evidence of the limited role of the baroreflex in the autonomic responses to CFT. They suggest that the CFT may be of use in assessing the integrity of the efferent cardiovascular autonomic pathways in patients with suspected baroreflex impairment.     

Baroreflex sensitivity and power spectral analysis during autonomic testing in different extrapyramidal syndromes

Autonomic dysfunction has been frequently demonstrated in patients with extrapyramidal diseases by cardiovascular autonomic testing. In addition to classical testing, we applied the more detailed baroreflex and spectral analysis on three traditional cardiovascular tests in this study to get additional information on autonomic outflow. We recorded continuously blood pressure, electrocardiogram, and respiration in 35 patients with multiple system atrophy, 32 patients with progressive supranuclear palsy, 46 patients with idiopathic Parkinson's disease and in 27 corresponding healthy subjects during cardiovascular autonomic testing (metronomic breathing, Valsalva manoeuvre, head‐up tilt). Baroreflex and spectral analyses were performed by using trigonometric regressive spectral analysis between and during the manoeuvres. Consistent with previous interpretations, our data showed an increase of sympathetic activity in head‐up tilt and Valsalva test in healthy controls. This sympathetic activity was significantly decreased in patients with typical and atypical Parkinson syndromes. Significant modulation of baroreflex activity could be observed especially during metronomic breathing; again it was significantly lower in all patient groups. Baroreflex and spectral parameters could not only differentiate between patients and healthy controls, but also differentiate between clinically symptomatic (with autonomic dysfunction as eg. orthostatic hypotension) and asymptomatic patients. In conclusion, our approach allows the evaluation of autonomic variability during short and nonstationary periods of time and may constitute a useful advance in the assessment of autonomic function in both physiological and pathological conditions. © 2009 Movement Disorder Society     

Heart rate and arterial pressure variability in the experimental renovascular hypertension model in rats

This study was conducted in one kidney, one clip (1K1C) Goldblatt hypertensive rats to evaluate vascular and cardiac autonomic control using different approaches: 1) evaluation of the autonomic modulation of heart rate (HR) and systolic arterial pressure (SAP) by means of autoregressive power spectral analysis 2) assessment of the cardiac baroreflex sensitivity; and 3) double blockade with methylatropine and propranolol. The 1K1C group developed hypertension and tachycardia. The 1K1C group also presented reduction in variance as well as in LF (0.23+/-0.1 vs. 1.32+/-0.2 ms2) and HF (6.6+/-0.49 vs. 15.1+/-0.61 ms2) oscillations of pulse interval. Autoregressive spectral analysis of SAP showed that 1K1C rats had an increase in variance and LF band (13.3+/-2.7 vs. 7.4+/-1.01 mmHg2) in comparison with the sham group. The baroreflex gain was attenuated in the hypertensive 1K1C (-1.83+/-0.05 bpm/mmHg) rats in comparison with normotensive sham (-3.23+/-0.06 bpm/mmHg) rats. The autonomic blockade caused an increase in the intrinsic HR and sympathetic predominance on the basal HR of 1K1C rats. Overall, these data indicate that the tachycardia observed in the 1K1C group may be attributed to intrinsic cardiac mechanisms (increased intrinsic heart rate) and to a shift in the sympathovagal balance towards cardiac sympathetic over-activity and vagal suppression associated to depressed baroreflex sensitivity. Finally, the increase in the LF components of SAP also suggests an increase in sympathetic activity to peripheral vessels.     

Baroreflex failure following radiation therapy for nasopharyngeal carcinoma

The authors present a 51-year-old man with right-sided nasopharyngeal carcinoma who was treated for regional lymph node involvement by bilateral radiation therapy of the neck. Six years later he presented with episodic complaints of headache, flushing, and palpitations accompanied by elevations of blood pressure. Examination of arterial baroreflex function indicated selective afferent carotid sinus denervation. Cross spectral analysis of spontaneous heart rate and blood pressure variability showed decreased arterial baroreflex sensitivity (6.5 ms/mm Hg). Twenty-four hour measurements of blood pressure and heart rate variability showed labile hypertension during normal daytime activities. Baroreflex failure in this patient probably represents a late complication of bilateral radiation therapy of the neck.     

Reflex control of sympathetic outflow and depressed baroreflex sensitivity following myocardial infarction

Reflex control of heart rate is frequently impaired following myocardial infarction. This is referred to as depressed baroreflex sensitivity. The aim of these experiments was to assess the function of other autonomic reflexes in dogs with depressed baroreflex sensitivity. Comparisons were made to dogs in whom baroreflex sensitivity was preserved or unchanged after myocardial infarction. Under chloralose-barbiturate anesthesia, reflex control of sympathetic outflow by the sinoaortic baroreceptors was determined by measurement of changes in systolic arterial pressure and efferent renal sympathetic nerve activity during infusion of phenylephrine. Following sinoaortic denervation, reflex control of sympathetic outflow by cardiac receptors with vagal afferent fibers was determined by measurement of changes in pulmonary capillary wedge pressure and renal nerve activity during blood volume expansion. Reflex decreases in renal nerve activity in response to increases in arterial pressure were similar in the two groups of dogs. In contrast, elevation of pulmonary capillary wedge pressure elicited significantly greater reflex decreases in renal nerve activity in dogs with depressed baroreflex sensitivity following myocardial infarction compared to dogs with preserved baroreflex sensitivity. Hemodynamic parameters and infarct sizes were similar in each group. In conclusion, activation of cardiac receptors with vagal afferent fibers elicited greater reflex inhibition of sympathetic outflow in dogs with depressed baroreflex sensitivity following myocardial infarction. These data suggest that these receptors are "sensitized". These results provide additional support for the hypothesis that depressed reflex control of heart rate following myocardial infarction is related to augmented afferent input from the left ventricle.     

Medullary and intrathecal injections of 17beta-estradiol in male rats

The following experiments were designed to investigate the role of estrogen in central autonomic nuclei on autonomic tone and reflex control of heart rate. Male Sprague-Dawley rats were anesthetized with sodium thiobutabarbital (100 mg/kg) and instrumented to record blood pressure and heart rate. Efferent vagal and renal nerve activities were recorded and used to assess changes in parasympathetic and sympathetic tone, respectively. The cardiac baroreflex was evoked using a single bolus injection of phenylephrine (0.1 mg/kg) both before and following either intrathecal injection of estrogen (0.5 microM; 1 microl) to influence sympathetic preganglionic neurons of the intermediolateral cell column or bilateral injection of estrogen (0.5 microM; 100 nl/side) into the nucleus tractus solitarius, rostral ventrolateral medulla or nucleus ambiguus. The cardiac baroreflex was significantly enhanced following both intrathecal and medullary injections of estrogen. Efferent vagal nerve activity was significantly increased following injection of estrogen into the nucleus tractus solitarius, nucleus ambiguus and the intrathecal space. Renal sympathetic nerve activity was significantly depressed following injection of estrogen into the nucleus tractus solitarius, rostral ventrolateral medulla and the intrathecal space. In all cases, simultaneous injection of estrogen with the selective estrogen receptor antagonist, ICI 182,780 (1 pM) blocked all previously observed changes in baroreflex function and autonomic tone. These results demonstrate a role for estrogen in the reflex control of heart rate and as a central modulator of autonomic tone in male rats.     

Mathematical modeling of cardiovascular coupling: Central autonomic commands and baroreflex control

The cross-correlation function (CCF) yields the correlation coefficient between spontaneous fluctuations of heart period and blood pressure as a function of the time shift between these variables. Two CCF patterns occur in humans: I) positive correlation between heart period and previous pressure values; II) negative correlation between heart period and subsequent pressure values. These patterns may result from the baroreflex and central autonomic commands (CAC), respectively. The aim of this study was to test this interpretation with a non-linear mathematical model of the human cardiovascular system. CAC were modeled as either phasic changes or random fluctuations of vagal and sympathetic activities with opposite sign. CCF pattern I resulted from baroreflex buffering of blood pressure changes elicited by vascular resistance fluctuations. When cardiac baroreflex control was absent or outweighed by CAC to the heart, simulations resulted in CCF pattern II only. In intermediate conditions when cardiac baroreflex interacted with CAC to the heart, CCF patterns I and II coexisted because the coupling between heart period and blood pressure varied with time. CAC to the heart decreased in magnitude the correlation coefficient and lengthened the time shift of CCF pattern I, thus apparently slowing and blunting baroreflex effects. Conversely, the baroreflex decreased in magnitude the correlation coefficient of CCF pattern II, thus blunting CAC effects. These results provide theoretical evidence in favor of application of the CCF analysis to investigate the balance between central autonomic and baroreflex cardiac control.     

Baroreflex sensitivity and responses to the Valsalva manoeuvre in subjects with diabetes mellitus.

Baroreflex sensitivity was measured in a group of diabetic patients from the slope of the regression of pulse interval on systolic arterial pressure, during elevation of pressure induced by phenylephrine. The response to Valsalva's manoeuvre was assessed in the same subjects. There was a good correlation between the two tests in the identification of patients with a parasympathetic autonomic disturbance, but measurements of baroreflex sensitivity were more readily quantifiable than were the responses to Valsalva's manoeuvre. Furthermore, baroreflex sensitivity could be measured in patients with sympathetic nervous dysfunction in whom vagal function could not be assessed by means of the Valsalva manoeuvre. Measurement of baroreflex sensitivity is likely to be suitable for longitudinal studies of the progress of diabetic autonomic neuropathy.     

Cardiovascular dysautonomia in fatal familial insomnia

Autonomic control of the cardiovascular system was assessed in two patients with Fatal Familial Insomnia. The diagnosis was confirmed at autopsy in patient 1. In the resting state blood pressure and heart rate were higher than controls in patient 1; plasma noradrenaline levels were elevated in both patients. Evaluation of cardiovascular reflexes indicated intact baroreflex pathways but with exaggerated blood pressure and biochemical responses to certain stimuli (postural change, Valsalva manoeuvre, isometric handgrip). There was no pressor response to intravenously infused noradrenaline, an increased response to atropine and diminished depressor and sedative effects to clonidine. Overall these results are indicative of an unbalanced autonomic control with preserved parasympathetic and higher background and stimulated sympathetic activity. These physiological, biochemical and pharmacological data, together with known neuro-pathological findings in this disorder, emphasize the possible role played by the thalamus in regulating autonomic control of cardiovascular function in man.     

Hemispheric influence on autonomic modulation and baroreflex sensitivity

Several studies suggest hemispheric lateralization of autonomic cardiovascular control. There is controversy regarding which hemisphere dominates sympathetic or parasympathetic activity. Hemispheric influences on baroreflex sensitivity (BRS) have not yet been evaluated. To determine hemispheric autonomic control in epilepsy patients, we assessed cardiovascular and baroreflex modulation before and during hemispheric inactivation. For 15 patients with drug-refractory epilepsy, we analyzed autonomic heart rate (HR) and blood pressure (BP) modulation and BRS before and during left and right intracarotid amobarbital procedure (IAP). After Blackman-Tukey spectral analysis, we calculated the low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF: 0.15-0.5 Hz) power of HR and BP as well as BRS as the LF transfer function gain between BP and HR. Right hemispheric inactivation induced a significant decrease of BP and an increase of HF power of HR and BP (p < 0.05). Left inactivation increased HR, BP, and LF power of both signals and decreased BRS by nearly 30% (p < 0.05). The results confirm previous IAP studies showing sympathetic lateralization in the right hemisphere and, moreover, demonstrate parasympathetic predominance and up-regulation of BRS in the left hemisphere. In epilepsy patients, unilateral electrical activity might derange autonomic balance between both hemispheres and contribute to cardiovascular dysregulation and sudden fatalities.     

Altered baroreflex responses in alpha7 deficient mice

The autonomic nervous system controls and coordinates several cardiovascular functions, including heart rate, arterial pressure, blood flow and vasomotor tone. Neuronal nicotinic acetylcholine receptors (nAChRs) are the interface between the nervous system and the cardiovascular system, but it is not known which nAChR subtypes regulate autonomic function in vivo. Nicotinic AChRs containing the alpha7 subunit are a candidate subtype in autonomic ganglia. Stimulation of these nAChRs can increase neurotransmitter release via presynaptic mechanisms, as well as mediate fast synaptic transmission via postsynaptic mechanisms. To investigate the role of the alpha7 nAChR subunit in cardiac autonomic function, we measured baroreflex-mediated responses in alpha7 null mice. Here we show that the alpha7 null mice have impaired sympathetic responses to vasodilatation, as sodium nitroprusside infusion triggered a 48% heart rate increase in wild type mice but only a 21% increase in the alpha7 nulls (P < 0.001). The mutant mice developed supersensitivity to adrenergic agonists, although norepinephrine release from sympathetic nerve terminals could be elicited through mechanisms alternative to nAChR stimulation. Baroreflex-mediated parasympathetic responses were normal in alpha7 null mice. The decreased baroreflex-mediated tachycardia in alpha7 mutant mice indicates that alpha7-containing nAChRs participate in the autonomic reflex that maintains blood pressure homeostasis. The alpha7 mutant mice may serve as a model of baroreflex impairment arising from autonomic dysfunction.