Twenty-four-hour ambulatory blood pressure and heart rate profiles in diagnosing orthostatic hypotension in Parkinson's disease and multiple system atrophy.

BACKGROUND AND PURPOSE: Twenty-four-hour ambulatory blood pressure and heart rate monitoring (24-h ABPM) can provide vital information on circadian blood pressure (BP) profiles, which are commonly abnormal in Parkinson's disease with and without autonomic failure (PD + AF and PD) and multiple system atrophy (MSA). Twenty-four-hour ABPM has not been directly compared between these disorders regarding cardiovascular autonomic function. Our aim was to determine the usefulness of 24-h ABPM with diary compared to head-up tilting (HUT) in diagnosing orthostatic hypotension (OH) in these patients. METHODS: Seventy-four patients (23 MSA, 18 PD + AF, 33 PD) underwent cardiovascular autonomic screening followed by 24-h ABPM with diary. Standing tests were included during 24-h ABPM. The sensitivity and specificity in detecting OH from the 24-h ABPM standing test were compared with HUT. RESULTS: There was no difference in OH during HUT between MSA and PD + AF (P > 0.05). There was a higher proportion of abnormal BP circadian rhythms in MSA and PD + AF compared to PD (P < 0.05) but not between MSA and PD + AF (P > 0.05). Patients were divided into groups with OH (OH+) and without OH (OH-) on HUT. Using the standing test during 24-h ABPM, a systolic BP fall of >20 mmHg showed a sensitivity and specificity of 82% and 100% (area under the curve 0.91, 95% confidence interval 0.84-0.98) in differentiating OH+ from OH-. CONCLUSIONS: Parkinson's disease with autonomic failure and MSA patients had similar circadian BP patterns suggesting that autonomic dysfunction influences abnormal BP circadian patterns similarly in these disorders. The higher sensitivity and specificity in detecting OH using a systolic BP fall of >20 mmHg compared to a diastolic BP fall of >10 mmHg during the standing test supports its usefulness to assess autonomic function in MSA and PD.

Non-dipping nocturnal blood pressure and psychosis parameters in Parkinson disease.

BACKGROUND: Non-motor symptoms are increasingly recognized in Parkinson disease (PD) and include physical as well as psychological symptoms. A psychological condition that has been well studied in PD is psychosis. Cardiovascular autonomic dysfunction in PD can include a reversed or loss of blood pressure (BP) circadian rhythm, referred to as nocturnal non-dipping. The aim of this study was to determine the relationship between 24 h ambulatory blood pressure measurements (ABPM), i.e., absence or presence of nocturnal dipping, and psychosis scores in PD. METHODS: Twenty-one patiens with PD underwent 24 h ABPM using an autonomic protocol. A decrease in nocturnal mean arterial blood pressure of less than 10% was defined as non-dipping. Patients were interviewed (including the brief psychiatric rating scale; BPRS) for the assessment of psychosis. RESULTS: Eleven patients were dippers and 10 were non-dippers. BPRS scores were higher in non-dippers, who, on average, met the criteria for psychosis (mean non-dipper BPRS: 34.3 ± 7.3 vs mean dipper BPRS: 27.5 ± 5.3; cutoff for "mildly ill" 31). There was a correlation between BPRS scores and non-dipping, indicating that those patients who had a blunted nocturnal fall in BP were more prone to psychotic symptoms (Pearson's Correlation = 0.554, p = 0.009). CONCLUSION: These results suggest that, among PD patients, a non-dipping circadian rhythm is associated with more severe symptoms of psychosis than is a dipping circadian rhythm. This association warrants further investigation.

Headache in three new cases of Harlequin syndrome with accompanying pharmacological comparison with migraine.

BACKGROUND: Harlequin syndrome (HS) is a rare autonomic disorder characterised by unilateral diminished sweating and flushing of the face in response to heat or exercise. Some patients with HS complain of headache. METHODS: We present three new cases to characterise their headache phenotype and pharmacology and review the literature of cases where headache was described. RESULTS Two out of the three patients presented with episodes of unilateral headache associated with exercise: in one case the headache had migrainous features and was contralateral to the side where the flushing occurred, whereas the second patient, who had had migraine attacks in the past, had a brief throbbing headache, with no associated symptoms, ipsilateral to the facial flushing. The third woman had migraine but the attacks were not associated with HS. Pharmacological characterisation suggested the HS and migraine were biologically distinct. HS was not triggered by nitroglycerin and was unaffected by sumatriptan, dihydroergotamine and ergotamine. HS and migraine did not occur together. In the literature, we found six patients with both HS and headache, five of whom had migraine. CONCLUSIONS: These data do not show any correlation between the phenotypic expression of migraine and HS suggesting the syndromes are pathogenetically independent.

Progression of cardiovascular autonomic dysfunction in Holmes-Adie syndrome.

The Holmes-Adie Syndrome (HAS) is a disorder of unknown aetiology comprising unilateral or bilateral tonic pupils with near light dissociation and tendon areflexia. Although considered to be benign, troublesome symptoms may result from autonomic disturbances, affecting vasomotor, sudomotor and respiratory function. It is unclear if the autonomic manifestations of the disease remain stable or progress, as longitudinal studies with detailed autonomic assessments have not been described. The authors report four HAS patients studied at intervals over 16, 8, 4 and 2 years with cardiovascular autonomic tests (head-up tilt, isometric exercise, mental arithmetic, cutaneous cold, deep breathing, Valsalva manoeuvre and standing). In each, there was progression of cardiovascular autonomic deficits with time, accompanied by symptomatic worsening. These observations in HAS, for the first time, indicate progression of cardiovascular autonomic dysfunction of clinical significance. This has a number of implications, including those relating to aetiology and prognosis. The authors recommend regular clinical and laboratory follow-up, especially of cardiovascular autonomic function, in patients with HAS.

Abnormal cardiovascular responses to carotid sinus massage also occur in vasovagal syncope - implications for diagnosis and treatment.

BACKGROUND AND PURPOSE: Carotid sinus massage (CSM) is commonly used to identify carotid sinus hypersensitivity (CSH) as a possible cause for syncope, especially in older patients. However, CSM itself could provoke classical vasovagal syncope (VVS) in pre disposed subjects. METHODS: Retrospective analysis of CSM, cardiovascular autonomic function tests (including tilt table testing) and medical history in 388 patients with recurrent syncope to identify and characterize patients in whom an abnormal response to CSM was more likely to reflect VVS than CSH. RESULTS: CSM was abnormal in 79 patients. In 53 patients (77.2 +/- 8.7 years), CSH was the likely cause of syncope. VVS was the more likely diagnosis in 26 younger patients (59.7 +/- 12.6 years) with longstanding syncope from youth, in whom fear or pain was as a trigger; 7/26 suffered from intense chronic or intermittent neck pain and one exacerbation of syncopal attacks followed a physical and emotional trauma to the neck. In VVS, 4/26 had spontaneous VVS during head-up tilt, another six after venepuncture (performed in 17/26). In 6/26, the abnormal response to CSM was delayed, occurring 62.8 +/- 28.4 s after completion of CSM. The response to CSM was predominantly of the mixed type (20/26) and abnormal on both sides in 14/26. CONCLUSIONS: An abnormal response to CSM may not indicate syncope caused by CSH and needs to be considered in the light of the patient's age, duration of syncopal episodes and detailed history of provocative stimuli. Differentiating CSH from VVS with an abnormal response to CSM has various implications from advice on driving to treatment strategies.

International spinal cord injury cardiovascular function basic data set.

OBJECTIVE: To create an International Spinal Cord Injury (SCI) Cardiovascular Function Basic Data Set within the framework of the International SCI Data Sets. SETTING: An international working group. METHODS: The draft of the data set was developed by a working group comprising members appointed by the American Spinal Injury Association (ASIA), the International Spinal Cord Society (ISCoS) and a representative of the executive committee of the International SCI Standards and Data Sets. The final version of the data set was developed after review by members of the executive committee of the International SCI Standards and Data Sets, the ISCoS scientific committee, ASIA board, relevant and interested international organizations and societies, individual persons with specific interest and the ISCoS Council. To make the data set uniform, each variable and each response category within each variable have been specifically defined in a way that is designed to promote the collection and reporting of comparable minimal data. RESULTS: The variables included in the International SCI Cardiovascular Function Basic Data Set include the following items: date of data collection, cardiovascular history before the spinal cord lesion, events related to cardiovascular function after the spinal cord lesion, cardiovascular function after the spinal cord lesion, medications affecting cardiovascular function on the day of examination; and objective measures of cardiovascular functions, including time of examination, position of examination, pulse and blood pressure. The complete instructions for data collection and the data sheet itself are freely available on the websites of both ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org).

Neural activity in the human brain relating to uncertainty and arousal during anticipation.

We used functional magnetic resonance neuroimaging to measure brain activity during delay between reward-related decisions and their outcomes, and the modulation of this delay activity by uncertainty and arousal. Feedback, indicating financial gain or loss, was given following a fixed delay. Anticipatory arousal was indexed by galvanic skin conductance. Delay-period activity was associated with bilateral activation in orbital and medial prefrontal, temporal, and right parietal cortices. During delay, activity in anterior cingulate and orbitofrontal cortices was modulated by outcome uncertainty, whereas anterior cingulate, dorsolateral prefrontal, and parietal cortices activity was modulated by degree of anticipatory arousal. A distinct region of anterior cingulate was commonly activated by both uncertainty and arousal. Our findings highlight distinct contributions of cognitive uncertainty and autonomic arousal to anticipatory neural activity in prefrontal cortex.

Effects of water drinking on cardiovascular responses to supine exercise and on orthostatic hypotension after exercise in pure autonomic failure.

OBJECTIVE: Patients with pure autonomic failure (PAF) have an abnormal fall in blood pressure (BP) with supine exercise and exacerbation of orthostatic hypotension (OH) after exercise. This study assessed the pressor effect of water on the cardiovascular responses to supine exercise and on OH after exercise. METHODS: 8 patients with PAF underwent a test protocol consisting of standing for 5 min, supine rest for 10 min, supine exercise by pedalling a cycle ergometer at workloads of 25, 50 and 75 W (each for 3 min), supine rest for 10 min and standing for 5 min. The test protocol was performed without water ingestion and on a separate occasion after 480 ml of distilled water immediately after pre-exercise standing. Beat to beat cardiovascular indices were measured with the Portapres II device with subsequent Modelflow analysis. RESULTS: All patients had severe OH pre-exercise (BP fall systolic 65.0 (26.1) mm Hg, diastolic 22.7 (13.5) mm Hg), with prompt recovery of BP in the supine position. 5 min after water drinking, there was a significant rise in BP in the supine position. With exercise, there was a clear fall in BP (systolic 42.1 (24.4) mm Hg, diastolic 25.9 (10.0) mm Hg) with a modest rise in heart rate; this occurred even after water ingestion (BP fall systolic 49.8 (18.9) mm Hg, diastolic 26.0 (9.1) mm Hg). BP remained low after exercise but was significantly higher after water intake, resulting in better tolerance of post-exercise standing. CONCLUSIONS: Water drinking did not change the abnormal cardiovascular responses to supine exercise. However, water drinking improved orthostatic tolerance post-exercise.

Neuroanatomical basis for first- and second-order representations of bodily states.

Changes in bodily states, particularly those mediated by the autonomic nervous system, are crucial to ongoing emotional experience. A theoretical model proposes a first-order autoregulatory representation of bodily state at the level of dorsal pons, and a second-order experience-dependent re-mapping of changes in bodily state within structures such as cingulate and medial parietal cortices. We tested these anatomical predictions using positron emission tomography and a human neurological model (pure autonomic failure), in which peripheral autonomic denervation prevents the emergence of autonomic responses. Compared to controls, we observed task-independent differences in activity of dorsal pons and context-induced differences in cingulate and medial parietal activity in PAF patients. An absence of afferent feedback concerning autonomically generated bodily states was associated with subtle impairments of emotional responses in PAF patients. Our findings provide empirical support for a theory proposing a hierarchical representation of bodily states.

Progression of dysautonomia in multiple system atrophy: a prospective study of self-perceived impairment.

To assess severity and progression of self-perceived dysautonomia and their impact on health-related quality of life (Hr-QoL) in multiple system atrophy (MSA), twenty-seven patients were recruited by the European MSA Study Group (EMSA-SG). At baseline, all patients completed the Composite Autonomic Symptom Scale (COMPASS) and the 36 item Short Form Health Survey (SF-36), and they were assessed using the 3-point global disease severity scale (SS-3) and the Unified MSA Rating Scale (UMSARS). After 6 months follow-up, the self completed COMPASS Change Scale (CCS), the SF-36, SS-3, and UMSARS were obtained. MSA patients showed marked self-perceived dysautonomia at baseline visit and pronounced worsening of dysautonomia severity on the CCS at follow-up. Severity and progression of dysautonomia did not correlate with age, disease duration, motor impairment and overall disease severity at baseline. There were no significant differences between genders and motor subtypes. Baseline COMPASS scores were, however, inversely correlated with SF-36 scores. Progression of self-perceived dysautonomia did not correlate with global disease progression. Hr-QoL scores were stable during follow-up. This is the first study to investigate self-perceived dysautonomia severity in MSA and its evolution over time. Our data suggest that dysautonomia should be recognized as a key target for therapeutic intervention in MSA.

Unexplained syncope--is screening for carotid sinus hypersensitivity indicated in all patients aged >40 years?

OBJECTIVE: To determine the frequency, age distribution and clinical presentation of carotid sinus hypersensitivity (CSH) among 373 patients (age range 15-92 years) referred to two autonomic referral centres during a 10-year period. METHODS: Carotid sinus massage (CSM) was performed both supine and during 60 degree head-up tilt. Beat-to-beat blood pressure, heart rate and a three-lead electrocardiography were recorded continuously. CSH was classified as cardioinhibitory (asystole > or = 3 s), vasodepressor (systolic blood pressure fall > or = 50 mm Hg) or mixed. All patients additionally underwent autonomic screening tests for orthostatic hypotension and autonomic failure. RESULTS: CSH was observed in 13.7% of all patients. The diagnostic yield of CSM was nil in patients aged < 50 years (n = 65), 2.4% in those aged 50-59 years (n = 82), 9.1% in those aged 60-69 years (n = 77), 20.7% in those aged 70-79 years (n = 92) and reached 40.4% in those > 80 years (n = 57). Syncope was the leading clinical symptom in 62.8%. In 27.4% of patients falls without definite loss of consciousness was the main clinical symptom. Mild and mainly systolic orthostatic hypotension was recorded in 17.6%; evidence of sympathetic or parasympathetic dysfunction was found in none. CONCLUSIONS: CSH was confirmed in patients > 50 years, the incidence steeply increasing with age. The current European Society of Cardiology guidelines that recommend testing for CSH in all patients > 40 years with syncope of unknown aetiology may need reconsideration. Orthostatic hypotension was noted in some patients with CSH, but evidence of sympathetic or parasympathetic failure was not found in any of them.

Long-term outcome of high-dose melphalan and autologous stem cell transplantation for AL amyloidosis.

Light chain (AL) amyloidosis is the result of a clonal plasma cell expansion, in which amyloidogenic monoclonal light chains deposit in various tissues resulting in organ dysfunction and organ failure. The median survival of patients with AL amyloidosis without therapy is 10-14 months. Several phase II studies report haematological and clinical remission in up to 50% of patients after high-dose melphalan and autologous stem cell transplantation. We analysed retrospectively the long-term outcome of 19 patients treated in this way between August/1996 and December/2001. We observed a relatively high treatment-related mortality of 26%, but 12 patients (63%) were high-risk candidates. Eight patients (42%) surviving longer than 100 days achieved haematological remission and long-term survival, whereas 6 (32%) obtained no clear benefit from high-dose therapy. However, 62% of patients survived beyond 2 years and the median survival from transplant was 48 months (range 0-104 months).

Skin vasomotor reflex responses in two contrasting groups of autonomic failure: multiple system atrophy and pure autonomic failure.

BACKGROUND & AIM: A variety of stimuli such as deep inspiration, isometric exercise and mental arithmetic, result in a transient vasoconstriction,mediated by sympathetic efferent nerves, in the skin of the fingers and toes of healthy controls (Skin Vasomotor Reflex: SkVR). Multiple system atrophy (MSA) and pure autonomic failure (PAF) provide contrasting models of autonomic failure. In MSA the lesion is central and preganglionic, whilst in PAF the lesion site is peripheral and postganglionic. We evaluated the SkVR in response to various stimuli in MSA and PAF, to determine differences in skin vasomotor involvement between these two patient groups. METHODS: 25 subjects (10 MSA, 7 PAF, 8 healthy controls) were studied. Baseline recordings of skin blood flow were obtained with a laser Doppler probe on the left index finger pulp and forearm. The subject then underwent a variety of stimuli with rest periods in between to reestablish baseline SkBF. These stimuli were: single deep inspiration (inspiratory gasp); mental arithmetic; bilateral leg elevation and cutaneous cold. RESULTS: Healthy control subjects demonstrated marked SkVRs on the finger pulp to each of the stimuli of a magnitude similar to those seen in previous studies, but no SkVRs on the forearm. In MSA SkVRs to inspiratory gasp on the finger pulp were reduced relative to controls. In PAF SkVRs were reduced relative to controls or MSA. The magnitude of SkVR response to gasp and cutaneous cold in PAF was significantly less than in healthy controls. In addition, the magnitude of the response in PAF was significantly less than in MSA for inspiratory gasp. CONCLUSIONS: PAF showed a decreased SkVR response to all 4 stimuli, the response being significantly less than controls (for inspiratory gasp and cutaneous cold) or MSA (cutaneous cold inspiratory gasp). The decreased responses in PAF may reflect the extensive postganglionic sympathetic denervation seen in this group. The measurement of SkVR may therefore provide a non-invasive aid to the differentiation of MSA and PAF.

EFNS guidelines on the diagnosis and management of orthostatic hypotension.

Orthostatic (postural) hypotension (OH) is a common, yet under diagnosed disorder. It may contribute to disability and even death. It can be the initial sign, and lead to incapacitating symptoms in primary and secondary autonomic disorders. These range from visual disturbances and dizziness to loss of consciousness (syncope) after postural change. Evidence based guidelines for the diagnostic workup and the therapeutic management (non-pharmacological and pharmacological) are provided based on the EFNS guidance regulations. The final literature research was performed in March 2005. For diagnosis of OH, a structured history taking and measurement of blood pressure (BP) and heart rate in supine and upright position are necessary. OH is defined as fall in systolic BP below 20 mmHg and diastolic BP below 10 mmHg of baseline within 3 min in upright position. Passive head-up tilt testing is recommended if the active standing test is negative, especially if the history is suggestive of OH, or in patients with motor impairment. The management initially consists of education, advice and training on various factors that influence blood pressure. Increased water and salt ingestion effectively improves OH. Physical measures include leg crossing, squatting, elastic abdominal binders and stockings, and careful exercise. Fludrocortisone is a valuable starter drug. Second line drugs include sympathomimetics, such as midodrine, ephedrine, or dihydroxyphenylserine. Supine hypertension has to be considered.

Multiple system atrophy and autonomic failure.

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that affects adults. It is characterised by autonomic failure affecting many systems; cardiovascular, urinary, sexual, gastrointestinal and sudomotor, amongst others. In addition there are motor deficits, resulting in both parkinsonian and/or cerebellar features. This review will outline the clinical features, investigations and management of MSA, with a particular emphasis on autonomic failure.

Neural activity relating to generation and representation of galvanic skin conductance responses: a functional magnetic resonance imaging study.

Central feedback of peripheral states of arousal influences motivational behavior and decision making. The sympathetic skin conductance response (SCR) is one index of autonomic arousal. The precise functional neuroanatomy underlying generation and representation of SCR during motivational behavior is undetermined, although it is impaired by discrete brain lesions to ventromedial prefrontal cortex, anterior cingulate, and parietal lobe. We used functional magnetic resonance imaging to study brain activity associated with spontaneous fluctuations in amplitude of SCR, and activity corresponding to generation and afferent representation of discrete SCR events. Regions that covaried with increased SCR included right orbitofrontal cortex, right anterior insula, left lingual gyrus, right fusiform gyrus, and left cerebellum. At a less stringent level of significance, predicted areas in bilateral medial prefrontal cortex and right inferior parietal lobule covaried with SCR. Generation of discrete SCR events was associated with significant activity in left medial prefrontal cortex, bilateral extrastriate visual cortices, and cerebellum. Activity in right medial prefrontal cortex related to afferent representation of SCR events. Activity in bilateral medial prefrontal lobe, right orbitofrontal cortex, and bilateral extrastriate visual cortices was common to both generation and afferent representation of discrete SCR events identified in a conjunction analysis. Our results suggest that areas implicated in emotion and attention are differentially involved in generation and representation of peripheral SCR responses. We propose that this functional arrangement enables integration of adaptive bodily responses with ongoing emotional and attentional states of the organism.

High prevalence of autoantibodies to glutamic acid decarboxylase in long-standing IDDM is not a marker of symptomatic autonomic neuropathy.

Immune reactivity to the enzyme glutamic acid decarboxylase (GAD), a pancreatic islet autoantigen, is present at the diagnosis of insulin-dependent diabetes mellitus (IDDM). Because GAD is also highly expressed in the nervous system, we investigated the presence of autoantibodies to the isoform GAD65 in patients with diabetic neuropathy, which is a debilitating complication of the disease. We studied 39 patients with autonomic and somatic neuropathy, 28 patients matched for age and IDDM duration, and 13 patients with a shorter duration of IDDM, all with no diabetic complications, as well as 50 recently diagnosed diabetic patients, 23 neurologic patients with idiopathic autonomic failure unrelated to IDDM, and 72 healthy subjects. An immunoprecipitation radioligand assay was used to detect anti-GAD65 autoantibodies with in vitro transcribed and translated human islet GAD65 as antigen. Autoantibodies to GAD65 were present in 56% of the diabetic patients with neuropathy, 57% of the long-duration and 69% of the short-duration diabetic control subjects, 78% of the recently diagnosed patients, and 13% of the nondiabetic neuropathic patients. Among the diabetic patients with neuropathy, there was no correlation between the presence of anti-GAD65 antibodies and the presence of autoantibodies to sympathetic ganglia, vagus nerve, or adrenal medulla structures identified by immunofluorescence. Our study shows that anti-GAD65 antibodies are present in a high proportion of patients with diabetic neuropathy but are not exclusively associated with it, rendering it unlikely that they have a role as a disease marker or that they are pathogenetic.(ABSTRACT TRUNCATED AT 250 WORDS)

Scintigraphic detection of coronary artery thrombi in patients with acute myocardial infarction.

To determine whether coronary thrombi can be detected scintigraphically after acute myocardial infarction, 24 patients were studied with a new method employing indium-111-labeled platelets and technetium-99m-labeled red blood cells. Nine patients with suspected infarction were evaluated initially within 9 hours of the onset of symptoms and again 18 to 24 hours after onset. Eight patients with neurologic symptoms but without overt cardiac disease and seven patients with angina but without infarction served as unmatched control subjects. Foci of net indium accumulation were detected after image processing that incorporated subtraction of blood pool activity. Carotid and pulmonary artery reference regions, in which blood pool activity is high and active platelet deposition unlikely, were used to correct digitized cardiac scintigrams for indium-111 platelet activity in the blood pool. In patients with infarction, distinct foci of net indium accumulation were present in regions corresponding to the coronary artery supplying ischemic zones. This occurred in seven of eight patients at the time of the earliest evaluation (5.6 +/- 3.3 hours [mean +/- SD] after the onset of symptoms) and in eight of nine patients at the time of subsequent imaging (23.6 +/- 1.9 hours after onset). Only 1 of the 15 control patients exhibited a cardiac focus of net indium accumulation. The percent of indium excess (100 [total indium-111 activity-blood pool indium-111 activity]/blood pool indium-111 activity) within the cardiac region measured (+/- SD) 16.8 +/- 11.6% in all patients with myocardial infarction (19.1 +/- 11.2% in those with visually identified foci) compared with 0.4 +/- 4.3% in control patients (p less than 0.001). This method permits early detection and sequential assessment of coronary artery thrombi. It should permit improved characterization of the role of platelets in the pathogenesis of acute manifestations of coronary vascular disease and improved evaluation of interventions designed to prevent or lyse coronary thrombi.

Dopamine beta-hydroxylase release during hypertension from sympathetic nervous overactivity in man.

In subjects with cervical spinal cord transections, hypertension due to sympathetic nervous overactivity resulted in a rise in plasma dopamine beta-hydroxylase (DbetaH), the peak occurring 3 to 5 min after the peak blood pressure response. This indicates that DbetaH may be released from sympathetic nerve terminals during sympathetic activity in man, and emphasizes the importance of sample timing in acute studies on DbetaH.

Role of sympathetic efferent nerves in blood pressure regulation and in hypertension.

This article presents some aspects of the role of sympathetic efferent nerves in the regulation of blood pressure in humans. Lessons have been learned from disorders that cause either sympathetic underactivity or overactivity. In chronic autonomic failure, pressor stimuli (mental arithmetic, isometric exercise, or cold) are unable to raise blood pressure, whereas stimuli that normally activate sympathetic efferent nerves to maintain blood pressure (head-up tilt, exercise, and food ingestion) can cause marked hypotension. Recognition of specific defects, such as the inability to synthesize norepinephrine in isolated dopamine beta-hydroxylase deficiency, suggests that sympathetic nerves may influence blood pressure regulation through nonadrenergic mechanisms (dopamine, neuropeptides, and purines). Tetraplegic patients with high cervical cord transection also have sympathetic impairment and postural hypotension, but this is less of a clinical problem because of compensatory hormonal and other mechanisms. Tetraplegic patients are unique as they also may have severe paroxysmal hypertension because of increased spinal sympathetic reflex activity. The pathophysiological mechanisms responsible for this exaggerated response include changes in postsynaptic adrenergic receptor numbers and their sensitivity, the actions of nonadrenergic cotransmitters, and the lack of sympathoneural pathways from the brain that are severed by the lesion. Finally, the putative role of the sympathetic nervous system in hypertension with unilateral renal artery stenosis, which initially is humorally mediated, is discussed. The centrally acting sympatholytic agent clonidine is effective in lowering blood pressure in renovascular hypertension independently of humoral factors when multiple agents have failed.(ABSTRACT TRUNCATED AT 250 WORDS)