Plasma catecholamines and renin during operant blood pressure conditioning in baboons

Plasma catecholamines and renin activity were measured in baboons undergoing operant diastolic blood pressure conditioning. Pre-training baseline norepinephrine averged 364 pg/ml, epinephrine 253 pg/ml, dopamine 270 pg/ml, and renin activity 2.62 ng/ml/hr. During the training sessions, systolic blood pressure increased significantly 19 mmHg (15%), diastolic pressure 20 mmHg (30%), and heart rate 33 bpm (33%) compared with pre-session values. Also during the sessions, norepinephrine increased significantly by 253 pg/ml (48%) and epinephrine increased by 130 pg/ml (0.05<p<0.10), while plasma dopamine and renin activity did not change significantly. Plasma norepinephrine levels correlated positively with systolic and diastolic blood pressures in all baboons tested, in both baseline and training conditions. To the extent that plasma norepinephrine reflects sympathetic nervous system activity, these findings demonstrate an association between sympathetic activity and blood pressure in this hypertensive model.     

Sympathetic response to maximal bicycle exercise before and after leg strength training

Summary Plasma catecholamine concentrations at rest and in response to maximal exercise on the cycle ergometer (278±15 watts, 6 min duration) have been measured on seven young active male subjects (19±1 years old; 80±3 kg; 176±3 cm) prior to and after a eight week leg strength training program (5RM, squat and leg press exercise). Strength training resulted in a significant increase in performance on squat (103±3 to 140±5 kg) and leg press exercise (180±9 to 247±15 kg) associated with a small significant increase in lean body mass (64.5±2.2 to 66.3±2.1 kg) and no change in maximal oxygen consumption (47.5±1.3 to 46.9±1.2 ml · kg^–1 · min^–1). Plasma norepinephrine (NE) and epinephrine (E) concentrations (pg · mL^–1) were not significantly different before and after training at rest (NE: 172±19 vs 187±30; E: 33±10 vs 76±16) or in response to maximal exercise (NE: 3976±660 vs 4163±1081; E: 1072±322 vs 1321±508). Plasma lactate concentrations during recovery were similar before and after training (147±5 vs 147±15 mg · dL^–1). Under the assumption that the central command is reduced for a given absolute workload on the bicycle ergometer following leg strength training, these observations support the hypothesis that the sympathetic response to exercise is under the control of information from muscle chemoreceptors.Supported by grants from NSERC, Government of Canada and FRSQ, Government of Quebec     

Contribution of catechol O-methyltransferase to the removal of accumulated interstitial catecholamines evoked by myocardial ischemia

Catechol O-methyltransferase (COMT) plays an important role for clearance of high catecholamine levels. Although myocardial ischemia evokes similar excessive catecholamine accumulation, it is uncertain whether COMT activity is involved in the removal of accumulated catecholamines evoked by myocardial ischemia. We examined how COMT activity affects myocardial catecholamine levels during myocardial ischemia and reperfusion. We implanted a dialysis probe into the left ventricular myocardial free wall and measured dialysate catecholamines levels in anesthetized rabbits. Dialysate catecholamine levels served as an index of myocardial interstitial catecholamine levels. We introduced myocardial ischemia by 60 min occlusion of the main coronary artery. The ischemia-induced dialysate catecholamines levels were compared with and without the pretreatment with entacapone (COMT inhibitor, 10 mg/kg, i.p.). Acute myocardial ischemia progressively increased dialysate catecholamine levels. Acute myocardial ischemia increased dialysate norepinephrine (NE) levels (20,453+/-7186 pg/ml), epinephrine (EPI) levels (1724+/-706 pg/ml), and dopamine (DA) levels (1807+/-800 pg/ml) at the last 15 min of coronary occlusion. Inhibition of COMT activity by entacapone augmented the ischemia-induced NE levels (54,306+/-6618 pg/ml), EPI levels (2681+/-567 pg/ml), and DA (3551+/-710 pg/ml) levels at the last 15 min of coronary occlusion. Myocardial ischemia evoked NE, EPI, and DA accumulation in the myocardial interstitial space. The inhibition of COMT activity augmented these increments in NE, EPI, and DA. These data suggest that cardiac COMT activity influences on the removal of accumulated catecholamine during myocardial ischemia.     

Sympathetic Neuronal Function and Left Ventricular Performance During Behavioral Stress in Humans: The Relationship between Plasma Catecholamines and Systolic Time Intervals

We studied the relationship between sympathetic neuronal function and left ventricular performance during stress in humans by analysis of endogenous catecholamine levels and systolic time intervals. The results showed that performance on a stressful cognitive task was accompanied by changes in plasma catecholamines, heart rate (HR), blood pressure (BP), and systolic time intervals. The cardiovascular responses were significantly correlated with plasma levels of epinephrine (E) and norepinephrine (NE). The relationship between plasma catecholamines and systolic time intervals is thought to reflect sympatho-adrenomedullary impact on left ventricular performance during stress.     

Renal handling of norepinephrine and epinephrine in the pig

To investigate the renal handling of catecholamines in the pig, intravenous infusions of⁵¹Cr-EDTA and PAH were performed in 7 animals, and samples for simultaneous measurement of norepinephrine (NE), epinephrine (E),⁵¹Cr-EDTA and PAH were obtained through catheters placed into the aorta, left renal vein and both urethers. For both kidneys together,⁵¹Cr-EDTA clearance [GFR] averaged 48±14 (±SD) ml/min (2.23±0.66 ml/kg/min). In the left kidney, GFR averaged 22±9 ml/min, arteriovenous PAH extraction 0.87±0.09, and calculated total renal plasma flow 91±30 ml/min. Plasma NE and E were lower in renal venous than arterial blood (P<0.005), extraction ratios averaging 0.36 and 0.77, respectively. NE excretion rate in final urine (8.9±4.3 ng/min) exceeded transrenal NE extraction rate (5.2±3.9 ng/min) by 3.7±4.4 ng/min. In contrast, urinary E excretion rate (2.9±2.0 ng/min) was slightly lower than transrenal E extraction rate (3.6±3.8 ng/min). These observations suggest that in pig kidneys, plasma PAH extraction rate and GFR related to body weight are quite similar to values in man. Three quarters of circulating E are extracted for the most part by tubular secretion, and the slightly smaller amount appearing in urine is consistent with some intrarenal metabolism. NE, presumably originating from intrarenal neuronal release and/or de novo production, is secreted into the urine.This study was supported by the Swiss National Science Foundation     

Stimulation of endogenous catecholamine release by theophylline: a proposed additional mechanism of action for theophylline effects

Therapeutic response to theophylline in asthma is generally attributed to its effect in increasing intracellular 3′,5′ cyclic adenosine monophosphate (cAMP) by competitive inhibition of cAMP phosphodiesterase. However, because of discrepancies between therapeutic serum theophylline concentration achieved clinically and those required for in vitro phosphodiesterase inhibition, we explored the possibility that theophylline may act through adrenomedullary secretion of catecholamines. Five healthy, nonasthmatic male and female adults were studied with a double-blind, randomized, crossover protocol. Theophylline (5 mg/kg) and placebo were administered in a capsule dosage form. Plasma catecholamines epinephrine (E), norepinephrine (NE), and dopamine (DA) were measured by a radioenzymatic assay at baseline and after administration of theophylline at 1, 2, and 3 hr. Significant differences between theophylline- and placebo-treated groups (p < 0.05) were seen at 3 hr for mean percentage increase over baseline with E (120% ± 25.3%) and NE (48.02% ± 17.94%) after theophylline therapy (mean peak level 7.2 ± 0.48 μg/ml). Epinephrine plasma concentration was significantly greater (p < 0.001) at 3 hr compared with baseline (105 ± 16 vs 56 ± 18 pg/ml), while NE (448 ± 52 vs 320 ± 36 pg/ml) did not attain significance (p = 0.136). A significant correlation (p < 0.05) was found between the percentage increase over basal for E (r = 0.58) and NE (r = 0.66) and serum theophylline levels. DA was not significantly increased at any time period. Thus theophylline in clinically relevant concentration appears to stimulate adrenomedullary secretion of catecholamine. Whether this is an important mechanism of action in asthma or explains some side effects of theophylline remains to be determined.     

Renal handling of dopa, dopamine, norepinephrine, and epinephrine in the dog

The uptake and excretion of endogenous dopa, dopamine, norepinephrine, and epinephrine by the kidney were studied. Blood samples were taken from the aorta at the origin of the renal artery and from the renal vein during a timed urine collection in each of six anesthetised greyhound dogs. Arterial plasma dopa (1,043 +/- 129 pg/ml) and epinephrine (218 +/- 96 pg/ml) were consistently higher than venous levels of dopa (591 +/- 80) and epinephrine (54 +/- 16 pg/ml), showing extraction of these by the kidney, whereas arterial plasma norepinephrine (329 +/- 89 pg/ml) and dopamine (64 +/- 9 pg/ml) were lower than the venous levels of norepinephrine (695 +/- 161 pg/ml) and dopamine (239 +/- 45 pg/ml), indicating secretion of these catecholamines into the circulation. The dopa extracted did not appear in the urine. Norepinephrine (7.2 +/- 1.7 ng/min), epinephrine (4.5 +/- 1.7 ng/min), and dopamine (3.2 +/- 0.7 ng/min) were excreted in the urine. These rates of urinary excretion could be accounted for by glomerular filtration and tubular secretion of the three catecholamines. The kidney extracts circulating dopa. It extracts and excretes epinephrine, norepinephrine, and dopamine, and, in addition, secretes both dopamine and norepinephrine into the circulation. These observations emphasize the important relationship between renal function and the peripheral sympathetic nervous system.     

Plasma catecholamine concentrations during a 72-hour aminophylline infusion in children with acute asthma

To explore the possibility that theophylline may act through adrenomedullary secretion of catecholamines, we examined the time courses of plasma norepinephrine (NE), epinephrine (E), and theophylline concentrations and peak expiratory flow (PEF) in nine children with an acute exacerbation of asthma receiving a 72-hour constant infusion of aminophylline. These measurements were made before (baseline) and at 2, 24, 48, and 72 hours after the infusion began. Plasma theophylline concentrations were kept constant in a near midpoint therapeutic range (mean +/- SEM, 14.1 +/- 1.3 to 16.1 +/- 1.1 micrograms/ml) during the 24- to 72-hour infusion periods. Compared with the respective baseline values (383.8 +/- 56.0 and 67.6 +/- 11.8 pg/ml for NE and E), the following postinfusion plasma catecholamines reached statistically significant difference: 664.0 +/- 125.1 pg/ml for NE at 24 hours (p less than 0.05), and 214.9 +/- 57.8, 233.7 +/- 82.2, and 137.6 +/- 39.4 pg/ml for E at 2, 24, and 48 hours (p less than 0.01). Despite the fact that similar plasma theophylline concentrations were maintained, plasma E, which peaked at 24 hours after dose, returned toward the baseline at the end of infusion (99.7 +/- 24.1 pg/ml), whereas this trend was not observed for NE. The postinfusion PEF increased (p less than 0.01) in a stepwise fashion, compared with the baseline, as the infusion progressed. The change in PEF correlated significantly (p less than 0.002) with plasma theophylline concentrations but not with the increase in plasma E from the baseline. Theophylline concentrations did not correlate with the increase in plasma NE or E from the baseline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of somatostatin on kidney function and vasoactive hormone systems in healthy subjects

Summary The acute effects of i.v. somatostatin (250 mcg bolus followed by 250 mcg/h continuous infusion for two hours) on renal hemodynamics, renal electrolyte and water handling, and urinary excretion of catecholamines and prostaglandins, as well as on plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, dopamine, glucagon, and plasma renin activity were studied in seven normal subjects. Somatostatin decreased effective renal plasma flow and glomerular filtration rate, osmotic and free water clearances, urine volume, and sodium and potassium excretion, while urinary osmolality, fractional excretion of sodium, and phosphate excretion increased significantly. Plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, and dopamine remained unchanged, while plasma renin activity (3.0±0.25 vs 2.4±0.2 ng AngI/ml/h;p}<0.01) and glucagon levels (40±11 vs 20±16 pg/ml;p}<0.01) decreased. Urinary excretion of norepinephrine, epinephrine, dopamine, PGE₂, and PGF_2alpha was suppressed under somatostatin. A significant positive correlation was found between urinary dopamine and sodium excretion (r=0.7;p}<0.001) and urinary postaglandin E₂ and glomerular filtration (r=0.52;p}<0.01). Without accompanying changes in plasma osmolality and vasopressin concentration significant antidiuresis occurred, suggesting a direct tubular effect of somatostatin. However, the hormone-induced changes are due mainly to the decrease in renal plasma flow. The results demonstrate that somatostatin at supraphysiological doses exerts significant effects on the kidney.Abbreviations PAH paraaminohippuric acid - ANF atrial natriuretic factor - AVP arginine vasopressin - PRA plasma renin activity - ERPF effective renal plasma flow - GFR glomerular filtration rate - TRP tubular reabsorption of phosphate - NE norepinephrine - E epinephrine - DA dopamine - GH growth hormone     

Catecholamine levels in practitioners of the transcendental meditation technique

With the aim of evaluating the sympathetic-adrenal medulla system in subjects practicing transcendental meditation (TM), their plasma catecholamine levels were determined at two different times of day. The study group consisted of 19 subjects who regularly practice either TM or Sidhi-TM technique, with a control group made up of 16 healthy subjects who had not previously used any relaxation technique. Catecholamine plasma levels were determined by high performance liquid chromatography, at 0900 and 2000 h. Morning and evening norepinephrine (NE) levels and morning epinephrine (E) levels were significantly lower in the TM group than in the control subjects (morning NE levels, pg/ml, mean+/-S.E.: TM group 136.6+/-13.0, control 236.8+/-21.0, P=.0001; evening NE levels: TM group 119.7+/-10.8, control 175.6+/-17.4, P=.009; morning E levels, pg/ml: TM group 140.2+/-10.6, control 196.7+/-23.8, P=.019). No differences were recorded for evening E levels and dopamine (DA) levels. No significant differences were found for catecholamine levels measured at different times of day in the TM group, demonstrating a lack of daily hormonal rhythm. Anxiety levels were similar in both groups. Based on the results obtained, it can be considered that the regular practice of TM has a significant effect on the sympathetic-adrenal medulla system. A low hormonal response to daily stress caused by sympathetic tone regulation through regular TM could explain our results, as well as the physiological and other effects related to the field of health described in those who practice meditation.     

Reproducibility of plasma catecholamine concentrations at rest and during exercise in man

Summary The purpose of this study was to test the reproducibility of plasma norepinephrine (NE) and epinephrine (E) concentrations, at rest and during exercise, in man. Twelve young men were evaluated on two occasions (one week apart) at rest in supine and sitting positions and during dynamic exercise on bicycle ergometer: 5 min at a low intensity workload (heart rate=131–133 bt min^–1) and 5 and 20 min at a higher intensity (174–175 bt min^–1). Mean plasma NE and E concentrations were not significantly different (p<0.05) on the two occasions in any of the experimental situations. However large within-subject variations were present, and the standard errors of a single measurement corrected for the variability of the catecholamine assay, ranged from 14 to 50% for NE and 14 to 37% for E. These results indicate that the mean plasma NE and E concentrations observed in a group of subjects are reproducible from one week to the other, but that individual plasma NE and E concentrations are not. This lack of reliability of a single determination of plasma catecholamine concentrations might be due to cyclic variations of plasma NE and E concentrations over time.Supported by grants from FCAC and FRSQ, Québec and NSERC, Canada.     

Plasma catecholamines associated with hypothalamically-elicited defense behavior

Sympatho-adrenal (SA) activation was determined by measuring levels of norepinephrine (NE) and epinephrine (E) in bilateral adrenal venous and peripheral venous plasma of 20 anesthetized cats following stimulation of medial hypothalamic sites. Hypothalamic sites were selected that elicited affective defense behavior in the freely moving cat. Fifty-eight percent of these hypothalamic sites elicited a bilateral increase greater than or equal to 10 ng/min in the output of both adrenal catecholamines (CAs); these increases were greater from the gland ipsilateral to the side of stimulation. Other SA responses included both preferential increases or decreases in either NE or E. Under baseline conditions, an average of 67% of the NE in the peripheral venous plasma was contributed by the sympathetic noradrenergic nerves; hypothalamic stimulation at "defense" sites increased the contribution to 75%. The data suggest that hypothalamic regions that elicit defense behaviour may overlap with regions that activate the adrenal medullary and sympathetic nervous systems.     

Blood sampling methodology is crucial for precise measurement of plasma catecholamines concentrations in mice

Epinephrine (E) and norepinephrine (NE) play a major role in regulating metabolism and cardiovascular physiology. Both are secreted in response to stress and their measurement in plasma allows the study of sympathoadrenal function. Several studies investigating sympathoadrenal physiology are conducted using mice. Review of the literature revealed that basal mouse NE and E plasma concentrations range within 4–140 nM depending on the blood sampling method. Such variability doesn't allow study comparison and may conceal catecholamine variations in response to stress. Therefore, our aim was to determine a reliable sampling method to measure mouse plasma catecholamine concentrations. Results showed that arterial catheterization is the most accurate sampling method: E and NE basal levels were similar to those found in humans (1.1±0.3 nM and 4.1±0.5 nM, respectively). Retro-orbital bleeding led to analogous results. On the contrary, decapitation was stressful for mice and consequently NE and E concentrations were high (24.6±2.7 nM and 27.3±3.8 nM, respectively). These different bleeding methods were compared in terms of their ability to detect sympathoadrenal system stimulation (cold-pressure test). With catheter and retro-orbital samplings the expected increase in NE and E levels was easily perceived. In contrast, with decapitation no significant change in E was detected. In conclusion, arterial-catheter and retro-orbital blood sampling methods appear to be the most accurate procedures for studying the sympathetic nervous system in mice in both unstressed and stressed conditions.     

Plasma-Katecholamin-Verlauf bei Alkylphosphat-Intoxikationen und deren Therapie

Summary In connection with the endogenous acetylcholine-poisoning due to organophosphorous compounds beside the clinical important muscarinic and nicotinic symptoms an activation of the sympathetic nervous system (adrenal medulla, sympathetic ganglia) is expected. Therefore a kinetic profile of norepinephrine and epinephrine in the plasma of two patients with severe parathionpoisonings was taken up through the whole period of the intensive-medical treatment. The method used was HPLC with electrochemical detection. The parathion-concentration of the same plasma samples were measured, too. The result were individual different courses with periodically appearing, markedly increased plasma catecholamine values. A direct correlation of catecholamines with the parathion-concentration was not recognizable. A possible influence of the atropine-treatment as well as of stress-factors is discussed but estimated as not responsible for the observed peaks.

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Abkürzungsverzeichnis Amp. Ampulle - ChE Cholinesterase - HPLC High pressure liquid chromatography (Hochdruckflüssig-Chromatographie) - Li Lithium - m-Rezeptoren muskarinische Rezeptoren - n-Rezeptoren nikotinische Rezeptoren - ® eingetragenes Warenzeichen - ZVD Zentraler Venendruck     

Fastigial stimulation in rats releases adrenomedullary catecholamines

Electrical stimulation of the rostral fastigial nucleus (FN) in anesthetized, paralyzed, and artificially ventilated rats with a 10-s stimulus train elicited a stimulus-locked elevation of arterial pressure (AP) and heart rate (HR) (the fastigial pressor response, FPR) and elevated plasma catecholamines (CA) within 20 s from the onset of stimulus. Norepinephrine (NE) increased from 139 +/- 24 to 280 +/- 43 pg/ml (P less than 0.05, n = 8) and epinephrine (E) from 70 +/- 26 to 360 +/- 107 pg/ml (P less than 0.02, n = 8). Acute adrenalectomy increased basal plasma NE (362 +/- 108 pg/ml, P less than 0.05, n = 6) and reduced E (9 +/- 4 pg/ml, P less than 0.02, n = 6). The magnitude and duration of the FPR and the relative increase of NE were unchanged; however, the elevation of E was abolished. Chemosympathectomy, produced by 6-hydroxydopamine hydrobromide (100 mg/kg iv, 24 h before the experiment), lowered resting AP (from 122 +/- 2 to 77 +/- 1 mmHg, P less than 0.001) and NE (16 +/- 5 pg/ml, P less than 0.01), but not E. After chemosympathectomy, FN stimulation induced a pressor response of greater magnitude and longer latency and duration than in controls, increased NE 3.5-fold (from 16 +/- 5 to 56 +/- 14 pg/ml, P less than 0.05, n = 5) and E 9-fold (from 38 +/- 11 to 336 +/- 88, P less than 0.05, n = 5). The increases in CA were abolished by adrenalectomy. Chemosympathectomy shifted the pressor-dose-response curves of NE and E to the left; thus, the enhanced pressor response to FN stimulation after chemosympathectomy was possibly a consequence of supersensitivity to circulatory CA. Stimulation of cerebellar FN increased plasma CA, as a consequence of coexcitation of both neural and adrenomedullary components of the autonomic nervous system. However, in rats with intact sympathetic nerves the release of adrenomedullary CA did not contribute to the elevation in AP.     

Immunohistochemical localization of epinephrine, norepinephrine, catecholamine-synthesizing enzymes, and chromogranin in neuroendocrine cells and tumors.

The immunohistochemical localization of epinephrine (E), norepinephrine (NE), and chromogranin was analyzed in normal and neoplastic neuroendocrine cells. The immunohistochemical detection of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) was used to distinguish between uptake and biosynthesis of catecholamines. E, NE, chromogranin, TH, DBH, and PNMT were found in the normal human adrenal medulla and in pheochromocytomas. Although many neuroendocrine tissues outside of the adrenal gland contained immunoreactive NE, only a small percentage of these tissues contained DBH. E was found in a few neuroendocrine tissues outside of the adrenal, including cardiac paragangliomas, and the enzyme PNMT was localized in some of these neoplasms. There was very close agreement between the localization of chromogranin and of catecholamines in normal and neoplastic neuroendocrine tissues. These results indicate that the presence of catecholamines and chromogranin in neuroendocrine cells and tumors within the adrenal medulla and in many other sites may be closely related.     

Responses of catecholamines and blood pressure to beta-blockade in diuretic-treated patients with essential hypertension

Summary Twenty patients (mean age 49±4 (SEM) yr) with mild to moderate essential hypertension were studied during placebo conditions, following 6 weeks of chlorthalidone monotherapy and 6 to 28 weeks of combined beta-blocker-chlorthalidone treatment, or vice versa. Compared to chlorthalidone therapy alone, addition of a beta-blocker to this diuretic caused a further blood pressure reduction in 11 patients (Responders); in 9 patients addition of a beta-blocking agent failed to further reduce blood pressure (Non-responders). Supine and upright plasma renin, aldosterone, norepinephrine and epinephrine levels and catecholamine excretion rates were always comparable between Responders and Non-responders. In both groups plasma and urinary norepinephrine or epinephrine values were not significantly altered following addition of a beta-blocker; heart rate and plasma renin activity were decreased in both groups to a similar extent. It is concluded that the antihypertensive mechanism of beta-blockers given to diuretic treated patients with essential hypertension is independant of renin and not associated with changes in plasma or urinary catecholamines.Supported in part by the Swiss National Science Foundation     

Plasma catecholamines and heart rate at the beginning of muscular exercise in man

Summary The relationship between the time course of heart rate and venous blood norepinephrine (NE) and epinephrine (E) concentrations was studied in 7 sedentary young men before and during 3 bicycle exercises of 5 min each (respectively 23±2.8%, 45±2.6% and 65±2.4% , mean ±SE). During the low level exercise the change in heart rate is monoexponential ( =5.7±1.2s) and no increment above the resting level of NE (NE) or of E (E) occurs. At the medium and highest intensity of exercise: a) the change in heart rate is biexponential, for the fast and the slow component averaging about 3 and 80 s respectively; b) NE (but not E) increases continuously with time of exercise; c) at the 5th min of exercise heart rate increments are related to NE; d) between 20s and 5 min, at corresponding sampling times, the heart rate of the slow component is linearly related to NE. At exercise levels higher than 33% the increase in heart rate described by the slow component of the biexponential kinetic could be due to an augmented sympathetic activity revealed by increased NE blood levels.     

Influence of sympatho-vagal balance on airway responsiveness in athletes

The increased prevalence of airway hyperresponsiveness (AHR) observed among athletes suggests that high-level training may contribute to the development of AHR. We investigated the possible influence of the sympatho-vagal balance on this phenomenon in 40 athletes and 10 sedentary controls. Each subject filled out a respiratory questionnaire, had a methacholine challenge, and measurements were made of their baseline plasma catecholamines [epinephrine (E), norepinephrine (NE) and dopamine (DA)] as a reflection of sympathetic tone, and their heart rate variability (SDNN: standard deviation of all normal-to-normal intervals) as an indicator of parasympathetic tone. The athletes had a 45% prevalence of AHR (defined as PC20 < 16 mg/ml, where PC20 is the concentration of methacholine inducing a 20% fall in the forced expiratory volume in 1 s, FEV1) with a mean PC20 of 21.2 mg/ml compared with 10% prevalence (mean PC20: 74.4 mg/ml) in sedentary subjects (P < 0.01). Plasma catecholamine values were not significantly different between the two groups (all P > 0.05), but the estimated parasympathetic tone was higher in athletes (P = 0.01). When data from all subjects were analyzed together, plasma E and NE correlated with PC20 (r = 0.39, P = 0.005 and r = 0.29, P < 0.005) but DA and SDNN did not (both P > 0.05). However, the ratios E/SDNN, NE/SDNN and DA/SDNN showed significant correlations with PC20 (r = 0.42, P < 0.01; r = 0.33, P < 0.005 and r = 0.31, P < 0.05, respectively) This study suggests that the sympatho-vagal balance may contribute to the increased AHR in the population studied but this influence alone cannot explain the higher prevalence of AHR in athletes.     

Peripheral catecholamine levels and the symptoms of anxiety: studies in patients with and without pheochromocytoma

We studied the correlation of plasma and urinary epinephrine (E) and norepinephrine (NE) levels with anxiety symptoms in three patient groups: 1) pheochromocytoma (PH+) (n = 17); 2) hypertensives with elevated catecholamine levels shown not to have a PH (PH-) (n = 25); and 3) patients with panic disorder (PD) (n = 23). Structured interviews and four self-rated anxiety scales were used: the SCL-90R Anxiety and Phobic Anxiety scales, and the Spielberger State/Trait Anxiety Inventories. The SCL-90R Somatization scale (which measures 12 somatic symptoms) was also utilized. None of the PH+ patients met DSM-III criteria for PD. Two met criteria for generalized anxiety disorder (GAD). Of the PH- patients, two had PD, two had GAD, and three had both. Urinary and plasma E did not show significant positive correlations with any of the four anxiety scales in any of the three patient groups. In both the PH+ and PH- groups, E was significantly correlated with the SCL-90R Somatization scale. NE was not significantly correlated with any of the four anxiety scales in the PH+ group. In contrast, in the PH- group, plasma NE was significantly correlated with anxiety on all anxiety scales (r = +0.55 to +0.77, p less than 0.05). Furthermore, in the PH- group, plasma NE was significantly correlated with those items of the SCL-90R Anxiety scale measuring the cognitive rather than the noncognitive symptoms of anxiety. In the PD group as well, plasma NE showed a significant correlation with the SCL-90R Anxiety Scale (r = +0.67, p less than 0.05). Taken together, our observations suggest that: 1) the effects of catecholamines in the periphery derived from a source independent of nervous system control (such as a PH) are not sufficient to elicit an anxiety disorder meeting DSM-III criteria; and 2) in patients without an autonomous source of peripheral catecholamines, NE in the periphery results from sympathetic nervous system activation and probably reflects, rather than causes, anxiety.