Hyperadrenergic State Research Articles

Alpha- and beta-adrenergic receptors in children with essential hypertension.

Platelet alpha 2- and lymphocyte beta-adrenergic receptors were examined in eight children aged 10-16 years with essential hypertension, and in 11 age-matched normotensive children. Both alpha 2- and beta-adrenergic receptor concentrations showed no significant differences between children with essential hypertension and normotensive children. According to other studies, physiological fluctuations in catecholamines determine lymphocyte beta-adrenergic receptor concentrations, although down-regulation in platelet alpha 2-adrenergic receptors has not been observed. The present findings suggest that there may be no abnormalities in alpha 2- and beta-adrenergic receptors in essential hypertension in childhood, although a hyperadrenergic state has been reported to be of some relevance to the pathogenesis of essential hypertension in young adolescents.

Mitral valve palpitations.

Few disorders ever provoked more interest and controversy than mitral valve prolapse (MVP). Past echocardiographic over-diagnosis led to it becoming a whipping boy for otherwise unexplained chest pain, palpitation, arrhythmias and emboli. Surgical centres reported a high incidence of endocarditis and severe regurgitation. Most investigators who have studied the prevalence of arrhythmias in MVP have concluded that they are more common in this syndrome than in the general population and that there is a causal rather than a fortuitous relationship. However, the prevalence of arrhythmias in reported studies is probably higher than in unselected MVP patients. Multiple ventricular premature beats, ventricular tachycardia and sudden death have been reported. Suggested mechanisms have included a focal cardiomyopathy with incoordinate contraction and relaxation, QRS dispersion, a long QT, traction on papillary muscles by prolapsed leaflets, interference with the blood supply of the papillary muscles, stimulation of the endocardium by the chordae and diastolic depolarisation of muscle fibres in redundant leaflets with triggered repetitive automaticity. MVP has been associated with pre-excitation giving rise to atrioventricular re-entry tachycardia. Autonomic dysfunction and a hyperadrenergic state has been claimed and this may also be responsible for supraventricular arrhythmias including atrioventricular nodal re-entry tachycardia, flutter and fibrillation. Electrophysiological studies have yielded contradictory results which may be due to the heterogeneity of the patients studied and variability of the mechanisms. Whatever the true prevalence, arrhythmias in MVP are usually benign. Syncope and sudden death are rare. Anti-arrhythmic therapy is only warranted in patients with frequent and distressing symptoms shown to be due to the arrhythmias or when arrhythmias are judged potentially life threatening.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperadrenergic states

To review the physiologic and pathophysiologic hyperadrenergic states and the pharmacologic use of sympathomimetic agents. Pharmacologic and physiologic studies in experimental animals and humans. Plasma catecholamines are increased in a variety of clinical situations. Following major injury, catecholamines act to support vital organ perfusion and mobilize fuel substrates. However, with surgical trauma and during acute medical illnesses, such as myocardial infarction, catecholamine-induced physiologic changes can interact with underlying disease processes to result in clinically significant complications. Exogenous catecholamines are used to treat a variety of medical conditions, including anaphylaxis and various shock states. Available sympathomimetic agents differ in their availability to stimulate different subpopulations of adrenergic receptors. These differences permit the astute clinician to achieve specific physiologic end-points. Finally, plasma catecholamines are increased in patients with pheochromocytoma. This latter condition provides insights into the long-term effects of catecholamine excess. Based on knowledge of the pharmacology of sympathomimetic agents and the physiologic consequences of adrenergic receptor stimulation, it is possible to prevent undesirable catecholamine effects and to utilize these agents to achieve desired therapeutic goals.

Altered β Adrenergic Receptor Function in Subjects with Symptomatic Mitral Valve Prolapse

Individuals with mitral valve prolapse (MVP) frequently show symptoms of a hyperadrenergic state. beta adrenergic receptor characteristics were compared in the lymphocytes of subjects with symptomatic MVP and control subjects during rest and exercise. At rest, the proportion of receptors binding agonist with high affinity, as determined from isoproterenol competition for (-)[125I]-iodopindolol binding sites, was greater in MVP subjects than in controls. With exercise, the proportion of high-affinity receptors in MVP subjects decreased to control levels. Isoproterenol stimulation of lymphocyte 3',5'-cyclic adenosine monophosphate (cyclic AMP) also was greater in MVP subjects than in controls at rest, but not during exercise. Plasma catecholamine concentrations in MVP subjects were normal during both rest and exercise. Unlike exercise, isoproterenol infusion elicited clinical manifestations of increased adrenergic responsiveness in MVP subjects. The beta receptor in exercised MVP subjects exhibited unusually high affinity agonist binding (i.e. a lower dissociation constant KH than in either the same subjects at rest or exercised controls) and also abnormal coupling to the stimulatory guanine nucleotide-binding regulatory protein (GS) of adenylate cyclase, as reflected by the inability of guanine nucleotide to convert the receptor to a low-affinity state. These findings suggest that functional alteration of the beta adrenergic receptor, in the absence of abnormal plasma catecholamine levels, might contribute to the hyperadrenergic state of MVP subjects at rest. However, desensitization of high affinity beta receptors or altered receptor-GS coupling might preserve normal adrenergic responsiveness during exercise.

The effect of hyperadrenergic states on platelet responsiveness to adrenaline: The role of leukocytes

The effect of hyperadrenergic states on platelet responsiveness to adrenaline: The role of leukocytes

Plasma Catecholamine Levels In Cyclic Antidepressant Overdose

Cyclic antidepressant overdose is a major cause of morbidity and mortality in self-poisoned patients. The major cause of mortality with cyclic antidepressant overdose is cardiotoxicity. We determined plasma catecholamine levels in 41 symptomatic acute overdose patients to identify interactions between QRS duration (a marker for cardiotoxicity) and a presumed hyper-adrenergic state. Using a linear multivariable regression analysis, QRS duration correlated with the presence of cyclic antidepressant, plasma norepinephrine levels, the ratio of norepinephrine to epinephrine level, and pulse rate (p less than 0.001, r2 = 0.42). Commensurate physiologic changes were not found in the presence of elevated catecholamine levels in the cyclic antidepressant overdose group. One possible explanation for the blunted systemic response to the elevated catecholamine levels is adrenergic desensitization. Investigation of serial catecholamine levels during cyclic antidepressant overdose may lead to modification of our current theories of cardiotoxicity and therapy.

Neurologic complications of cocaine abuse

The neurologic complications of cocaine toxicity are responsible for a major portion of the morbidity and mortality associated with cocaine. Most of the complications appear to be related to the hyperadrenergic state induced by cocaine and may be treated symptomatically. Diazepam is the most effective drug for cocaine-induced seizures.

Catecholamine-thyroid hormone interactions and the cardiovascular manifestations of hyperthyroidism

The spectrum of classic symptoms of hyperthyroidism suggests that in addition to the effects of increased thyroid hormone, affecting various organ systems, there is also a hyperadrenergic state. Despite this clinical impression, direct measures of serum levels of catecholamines and their urinary metabolites demonstrate values that are equal to or less than normal. In contrast, the hypothyroid patient who clinically manifests signs or decreased adrenergic stimulation can be expected to have increased levels of epinephrine, norepinephrine, and its metabolites. This review discusses possible mechanisms to explain this seeming paradox. Treatment of hyperthyroidism includes the rapid reversal of many of the adrenergic symptoms with use of β-blocking drugs. Return to a clinically and chemically euthyroid state, however, requires antithyroid therapy accomplished over a longer period of time. A knowledge of the interaction of the cardiovascular and extracardiovascular manifestations of hyperthyroidism and the role of the adrenergic nervous system is important in the rational management of these patients.

Role of noradrenaline in the pathogenesis of skin flap ischemic necrosis in the pig

Clinically, ischemic necrosis is one of the most common complications in skin flap surgery, but the etiology is still unclear. The objective of the present experiments was to study the important role of the locally released noradrenaline in the pathogenesis of ischemic necrosis in acute and delayed random pattern skin flaps (4 × 10 cm) raised on both flanks of the pig. In Experiment 1, it was observed that 93, 96, and 94% of the skin contents of noradrenaline were depleted in skin flaps delayed for 2, 4, and 14 days, respectively, compared to the acute skin flaps ( n = 8) raised in the same pig. Although the maximum depletion of noradrenaline in the delayed flaps occurred within 2 days of delay, significant ( P < 0.001) increase in the length of dye penetration in the delayed skin flaps was seen after 2 days of delay, compared to the acute skin flaps ( n = 12). In Experiments 2 and 3, 5 days of intravenous phenoxybenzamine treatment, starting 2 days preoperatively and at the doses of 0.25, 0.5, 1.0, or 1.5 mg/kg/day, did not have any significant effect on the skin blood flow ( n = 24) or viability (1 mg/kg/day; n = 32) in the acute skin flaps compared with the saline-treated control. Similarly, 5 days of intravenous phentolamine treatment (5 mg/kg/day) also did not have any significant effect on the skin blood flow ( n = 24) or viability ( n = 32) of acute skin flaps compared with the control. These results indicate that the hyperadrenergic state of the skin per se is unlikely a direct principal cause of skin flap ischemic necrosis in the pig.

Awareness of High Blood Pressure Stimulates Platelet Release Reaction

The present study aimed at testing the hypothesis of a link between mental stress and blood platelet function. Twenty-nine 19-year-old men were recruited from the 98th percentile of mean blood pressure (116 mmHg) at a routine medical screening. They were not informed about their elevated blood pressures at the time of the screening. One year later they were randomized into two groups. Group 1 (n = 16) was exposed to mental stress by a letter informing them about their high blood pressure, while group 2 (n = 13) was sent a neutral letter. At an examination 2 weeks later, heart rate (p less than 0.05) and plasma adrenaline (p less than 0.05) responses to a cold pressor test were exaggerated in the informed group. The plasma beta-thromboglobulin (beta TG) concentration was elevated in the informed group (p less than 0.05) as was mean blood pressure (p less than 0.05). beta TG correlated positively with hematocrit (r = 0.59, p less than 0.005) and mean blood pressure (r = 0.43, p less than 0.05), and negatively with plasma HDL (r = -0.61, p = 0.001). The study shows that awareness of hypertension induces a hyperadrenergic state which is associated with the platelet release reaction. Under these circumstances platelet release seems to be correlated to established coronary heart disease risk factors.

Symptomatic Mitral Valve Prolapse in Children and Adolescents: Catecholamines, Anxiety, and Biofeedback

It has been proposed that symptomatic mitral valve prolapse may be associated with a hyperadrenergic state and/or increased anxiety. To test this hypothesis, Spielberger State-Trait Anxiety (STAI) scores and 24-hour urinary catecholamine collections were gathered from 11 children and adolescents without mitral valve prolapse, 6 with asymptomatic mitral valve prolapse, and 14 who had chest pain (some with additional symptoms of shortness of breath, palpitations, and fatigue). STAI scores and catecholamine excretion values were not significantly different between groups. Ten symptomatic patients were randomly assigned to either eight sessions of skin temperature biofeedback with daily home practice of relaxation-mental imagery techniques or an attention-placebo condition. Change in 24-hour urinary catecholamine excretion values and STAI scores from baseline to end of treatment did not differ significantly between treatment and placebo conditions. Although not evident at the end of treatment, a significant decrease in chest pain was found in the biofeedback group at 6-month follow-up evaluation. In summary, results of this study did not show evidence of increased sympathetic tone or levels of anxiety in symptomatic pediatric patients with mitral valve prolapse. A behavioral treatment program using biofeedback and relaxation-mental imagery techniques was associated with decreased chest pain at 6-month follow-up.

Lactic acidosis in theophylline overdose

An 18-year-old man with theophylline overdose developed an increased anion gap metabolic acidosis. Serum lactate levels were markedly elevated. A direct correlation was found between the increasing theophylline level, clinical hyperadrenergic state, and the worsening acidosis. Early hemoperfusion reversed the acidosis, the elevated serum theophylline level, and the hyperadrenergic state. This case substantiates the role of lactate accumulation in the metabolic acidosis associated with isolated theophylline toxicity.

Cardiovascular pathophysiologic effects of cocaine on a superimposed hyperadrenergic state: G. L. Todd, D. J. Keller. Department of Anatomy, University of Nebraska Medical Center, Omaha, NE

Cardiovascular pathophysiologic effects of cocaine on a superimposed hyperadrenergic state: G. L. Todd, D. J. Keller. Department of Anatomy, University of Nebraska Medical Center, Omaha, NE

Systemic arterial hypertension in head trauma

The importance of maintaining adequate cerebral perfusion pressure to prevent cerebral ischemia is a well accepted concept in the management of patients with head injury. The potentially deleterious effects of too great a perfusion pressure, however, are generally less well appreciated. The occurrence of a hyperadrenergic state after head injury, and the effects of elevated blood pressure on the injured brain are reviewed, with emphasis placed on the pathophysiologic implications of a disturbance of the blood-brain barrier and of autoregulation in promoting brain swelling and formation of edema.

The beta-receptor, atheroma and cardiovascular damage

In man a close interrelationship exists between hyperadrenergic states, myocardial ischemia, necrosis, infarction and sudden cardiac death. Persistent high catecholamine levels may also be associated with increased vascular endothelial turnover and permeability to calcium and lipoproteins, increased blood velocity, abnormal blood flow patterns and atheroma formation. There are thus good reasons to predict a cardiovascular protective effect of beta-blockers. Animal data indicate that in spite of apparently adverse plasma lipoprotein changes beta-blockers retard atheromatous plaque formation under conditions of high cholesterol diet with or without stress. A slow heart rate, as well as a reduction in calcium influx and inhibition of both esterification of arterial wall cholesterol (by ACAT) and endothelial permeability to lipoproteins, may be central to this process. Beta-blockers benefit a spectrum of conditions related to the atheromatous process and myocardial necrosis. These are silent ischemia; stable (including mixed), unstable and preinfarction angina; periinfarction events (including myocardial rupture and dissection of the ascending aorta); and myocardial necrosis associated with stress conditions such as head injuries and subarachnoid hemorrhage. In one study coronary deaths in hypertensive men, particularly in smokers, were significantly reduced by metoprolol (a beta 1-selective blocker) compared to a diuretic. In contrast in the MRC study of mild hypertension only nonsmoking men with mild to moderate hypertension who received a nonselective beta-blocker appeared to experience fewer myocardial infarctions. Recent clinical data showed that moderate-severe hypertensives who were optimally controlled by atenolol-based treatment over a 10-year period were less likely to die from myocardial infarction than those suboptimally controlled, irrespective of a rise in serum triglyceride levels. Thus the net effect of acute beta-blockade in hyperadrenergic states, including myocardial infarction, is to limit cardiovascular damage. Chronic beta-blockade inhibits atheroma formation (in animals) and beneficially modifies the incidence of stroke and myocardial infarction, which in man are the long-term consequences of hypertension.

The heterogeneity of dopamine involvement in essential hypertension.

Compared to control subjects, patients with essential hypertension (EH) had a decreased urinary DA:NE ratio and an overall increase in the total (free + sulfated) plasma sum of NE, E and DA. With age-matching, this elevation was found to be due to augmented levels of DA sulfate. When subdivided into borderline (labile) and stable EH groups, only the borderline EH patients had heightened plasma DA sulfate levels, enhanced urinary homovanillic acid excretion and tended to have plasma NE and PRA increases. Patients with stable EH had a hyporesponsive urinary DA and Na+ excretion as well as reduced PRA levels at the height of furosemide-induced natriuresis. These data are compatible with a hyperdopaminergic component of the hyperadrenergic state, more or less affecting patients with borderline EH in contrast to the hypodopaminergic features of subjects evolving into stable EH in whom the neurogenic component subsides. In both EH subgroups, urinary DA lagged behind NE excretion. Dopaminergic tone may indirectly affect endogenous DA-modulated renal, adrenal and vascular synaptic processes as well as their responses to exogenous Angiotensin II and DA, respectively.

Role of neuropeptide Y (NPY) in cardiovascular responses to stress

Neuropeptide Y (NPY), a putative sympathetic neurotransmitter and neuromodulator, is released during sympathetic nerve stimulation and causes vasoconstriction and cardiodepression. Whether the release of NPY contributes to stress-induced cardiovascular responses was assessed by studying i) plasma levels of circulating NPY-immunoreactivity (NPY-ir) during various stress paradigms and ii) mechanisms of action of NPY in the cardiovascular system of the rat. Plasma NPY-ir was increased by all stress situations, such as transfer to a new environment (by 52%), exposure to cold water (4 degrees C) (by 117%) and hemorrhage (4 ml/300 g body weight) (by 231%). The cold water, stress-induced, maximal increase in circulating plasma NPY-ir was delayed in relation to the peak pressor response by 10-20 min. Administration of NPY caused dose-dependent pressor responses that were greater in pithed rats--which have all centrally mediated circulatory reflexes removed--than in conscious rats. Infusion of a low pressor (8.5 +/- 1.5 mm Hg) dose of norepinephrine into conscious rats potentiated NPY-mediated pressor responses 2-fold and also tended to increase bradycardic effect of a higher dose of NPY (by 19%). Thus hypertensive and bradycardiac actions of NPY appear to depend on the level of adrenergic activity and on the interactions at the level of vascular smooth muscle, heart, and baroreceptor reflexes. During a hyperadrenergic state such as stress, cardiovascular effects of NPY may be greatly accentuated. NPY may enhance and prolong the stress-induced hypertensive responses while antagonizing adrenergic cardiostimulation.

Myocardial hypertrophy: the effect of sodium and the role of sympathetic nervous system activity.

Dietary sodium and the myocardial alpha 1-receptor have been implicated in the hypertrophic response of myocardial tissue. Alterations in sodium homeostasis have been demonstrated to influence sympathetic nervous function, centrally and peripherally. In this investigation, we have examined the effect of dietary sodium on the development of myocardial hypertrophy; and the role of sympathetic neuroeffector mechanisms in the hypertrophic response. Studies were performed in three groups of uninephrectomized rats: A-regular diet; B-1% saline/regular diet; C-1% Saline/doca/regular diet. Groups A and B did not develop systemic hypertension (SHT). Saline treatment increased heart weight and the density of surface alpha 1-receptors; myocardial norepinephrine (NE) was reduced. Group C developed SHT. Heart weight was greatest in Group C; and myocardial NE was severely depleted. Downregulation of myocardial alpha 1-receptors, a finding consistent with the hyperadrenergic state, was observed in Group C. Our results suggest dietary sodium may modulate hypertrophic response in myocardial tissue, by altering sympathetic neuroeffector mechanisms.

A retrospective and explorative study of hypokalemia in psychiatric disorders: a beta 2-receptor related phenomenon.

Since the serum potassium level is under beta 2-adrenergic influence, we studied serum potassium values on admission in psychiatric patients. Data are reported on 683 patients from nine major diagnostic groups. Among these nine groups significant differences were found concerning the mean serum potassium level and incidence of hypokalemia. Significant differences existed between the alcohol withdrawal and attempted suicide groups compared to the dysthymic, bipolar manic, schizophrenic and nonschizophrenic psychosis groups. Like alcohol withdrawal, attempted suicide is assumed to be a hyper-adrenergic state. Although the relative contribution of factors like nutritional state, aldosterone, insulin, and beta 2-receptor density or sensitivity is unclear, the catecholamine-potassium relationship deserves further study.

Rebound Hypertension Following Abrupt Cessation of Clonidine and Metoprolol

Abrupt withdrawal of adrenergic blockers in a hypertensive subject may result in acute hypertensive crisis. This crisis results from marked increase in adrenergic discharge and upregulation of adrenoceptors. In a patient with hypertensive crisis following abrupt cessation of clonidine hydrochloride and metoprolol tartrate, intravenous administration of labetalol hydrochloride rapidly reduced blood pressure and heart rate to precrisis levels. The patient was subsequently maintained in a normotensive state by continued oral use of labetalol. This case study demonstrates that alpha- and beta-blocking activities of labetalol may be particularly beneficial in a hyperadrenergic state following abrupt withdrawal of adrenergic blockers.