Catecholamine Responses Research Articles

Effects of the IL-1 Receptor Antagonist on the IL-1- and Endotoxin-Induced Activation of the HPA Axis and Cerebral Biogenic Amines in Mice

Endotoxin (lipopolysaccharide, LPS) and interleukin-1 (IL-1) are known to activate the hypothalamo-pituitary- adrenocortical (HPA) axis, as well as brain norepinephrine (NE) and indoleamine metabolism. Because LPS administration is known to induce the synthesis and secretion of IL-1, it has been proposed that IL-1 is the endogenous mediator of the response to LPS. This proposal has been tested using various antagonists of IL-1 with varied results. Therefore we have re-examined this question using a wide range of doses of the interleukin-1- receptor antagonist protein (IL-1ra) at various times after intraperitoneal LPS. The results indicate that IL-1ra at doses more than adequate to prevent responses to exogenously administered IL-1β, failed to significantly attenuate the increases in plasma ACTH and corticosterone and the cerebral catecholamine and indoleamine responses induced by intraperitoneal LPS in mice. IL-1ra was also ineffective when plasma ACTH and corticosterone were measured at longer times after LPS, although some trends towards attenuations were occasionally observed at 4 or 6 h. The latter is consistent with the time course of IL-1 induction by LPS. Intracerebroventricular administration of IL-1ra attenuated the endocrine and neurochemical responses to intraperitoneal IL-1β. However, intracerebroventricular IL-1ra failed to antagonize the HPA and neurochemical responses to intraperitoneal administration of LPS or to intravenous IL-1β. In all of these experiments, there were very close parallels between the HPA and the neurochemical responses, especially that of NE. We conclude that IL-1 does not mediate the HPA or the neurochemical responses to intraperitoneal LPS, although it may contribute in a minor way to the late HPA responses. However, IL-1 within the CNS may contribute to the responses to intraperitoneal IL-1, but not to intraperitoneal LPS or intravenous IL-1.

Instantaneous orthostatic hypotension in children and adolescents: a new entity of orthostatic intolerance.

We are the first to report clinical characteristics and circulatory and catecholamine responses to postural change in 44 children with instantaneous orthostatic hypotension (INOH). The symptoms include chronic fatigue, orthostatic dizziness, weakness, sleep disturbance, syncope or near syncope, headache, and loss of appetite. We divided the patients into two groups: group I (30 patients) had either a recovery time for mean arterial pressure of >25 s or a recovery time of >20 s with a 60% or greater decrease in mean arterial pressure at the initial decrease; group II (14 patients) had a prolonged reduction in systolic arterial pressure of > 15% during the later stage of standing (3-7 min) in addition to the criteria for group I. INOH was characterized by a marked reduction in blood pressure at the initial decrease (mean, -55/-27 mm Hg systolic/diastolic). Delayed recovery time of >60 s was found in 21 of 44 patients and orthostatic tachycardia (>35 beats per minute) in 20 of 44. Plasma noradrenaline responses were significantly lower in group I and II than in controls at 1 min of standing and were lower in group II at 5 min of standing. These results suggest that mechanisms responsible for INOH may depend on insufficient sympathetic activation during standing, possibly due to centrally mediated sympathetic inhibition, thus causing impairment of quality of life including school absenteeism. INOH is an important pathologic condition in children with complaints of orthostatic intolerance and can be an unrecognized cause of chronic fatigue. This condition can be identified by using a noninvasive beat-to-beat continuous blood pressure monitoring system.

Distribution, functional role, and signaling mechanism of adrenomedullin receptors in the rat adrenal gland

Adrenomedullin (ADM) is a hypotensive peptide, highly expressed in the mammalian adrenal medulla, which belongs to a peptide superfamily including calcitonin gene-related peptide (CGRP) and amylin. Quantitative autoradiography demonstrated the presence of abundant [ 125I]ADM binding sites in both zona glomerulosa (ZG) and adrenal medulla. ADM binding was selectively displaced by ADM(22–52), a putative ADM-receptor antagonist, and CGRP(8–37), a ligand that preferentially antagonizes the CGRP1-receptor subtype. ADM concentration-dependently inhibited K +-induced aldosterone secretion of dispersed rat ZG cells, without affecting basal hormone production. Both ADM(22–52) and CGRP(8–37) reversed the ADM effect in a concentration-dependent manner. ADM counteracted the aldosterone secretagogue action of the voltage-gated Ca 2+-channel activator BAYK-8644, and blocked K +- and BAYK-8644-evoked rise in the intracellular Ca 2+ concentration of dispersed ZG cells. ADM concentration-dependently raised basal catecholamine (epinephrine and norepinephrine) release by rat adrenomedullary fragments, and again the response was blocked by both ADM(22–52) and CGRP(8–37). ADM increased cyclic-AMP release by adrenal-medulla fragments, but not capsule-ZG preparations, and the catecholamine response to ADM was abolished by the PKA inhibitor H-89. Collectively, the present findings allow us to draw the following conclusions: (1) ADM modulates rat adrenal secretion, acting through ADM(22–52)-sensitive CGRP1 receptors, which are coupled with different signaling mechanisms in the cortex and medulla; (2) ADM selectively inhibits agonist-stimulated aldosterone secretion, through a mechanism probably involving the blockade of the Ca 2+ channel-mediated Ca 2+ influx; (3) ADM raises catecholamine secretion, through the activation of the adenylate cyclase/PKA signaling pathway.

Blood pressure and plasma catecholamines in acute and prolonged hypoxia: effects of local hypothermia

This study measured the pressor and plasma catecholamine response to local hypothermia during adaptation to hypobaric hypoxia. Eight healthy men were studied at rest and after 10 and 45 min of local cooling of one hand and forearm as well as after 30 min of rewarming at sea level and again 24 h and 5 days after rapid, passive transport to high altitude (4,559 m). Acute mountain sickness scores ranged from 5 to 16 (maximal attainable score: 20) on the first day but were reduced to 0-8 by the fifth day. Systolic blood pressure, heart rate, and plasma epinephrine increased on day 1 at altitude compared with sea level but declined again on day 5, whereas diastolic and mean blood pressures continued to rise in parallel with plasma norepinephrine. With local cooling, an increased vasoactive response was seen on the fifth day at altitude. Very high pressures were obtained, and the pressure elevation was prolonged. Heart rate increased twice as much on day 5 compared with the other two occasions. Thoracic fluid index increased with cooling on day 5, suggesting an increase in pulmonary vascular resistance. In conclusion, prolonged hypoxia seems to elicit an augmented pressor response to local cooling in the systemic and most likely also the pulmonary circulation.

The molecular basis for distinct beta-adrenergic receptor subtype actions in cardiomyocytes.

Catecholamines exert physiologically important effects on the electrical properties and mechanical performance of the heart through the activation of adrenergic receptors. It has been 50 years since Ahlquist1 first postulated that the excitatory and inhibitory pressor responses to catecholamines must be mediated by distinct adrenergic receptors (ARs), then designated α (for excitatory) and β (for inhibitory). Ahlquist’s classification was expanded further by Lands et al,2 who recognized that both α- and β-ARs could be conveniently categorized into 2 distinct subtypes on the basis of their relative potencies for ligands available at that time. In the ensuing years, the predominant AR expressed by cardiomyocytes was shown to conform to the β1-AR subtype. Our understanding of the molecular basis for sympathetic modulation was advanced further by the observations that under normal physiological conditions catecholamines induce positive inotropic, chronotropic, and lusitropic (relaxant) responses in the heart through a β1-AR–activated pathway, which involves the stimulatory GTP regulatory protein (Gs), activation of adenylyl cyclase (AC), accumulation of cAMP, stimulation of cAMP-dependent protein kinase A (PKA), and phosphorylation of key target proteins (including the L-type calcium channel [ I Ca,L], phospholamban [PLB], and troponin I [TNI]). Potential contributions of other AR subtypes to the mechanism(s) of catecholamine action in the heart were largely ignored in early studies. However, the traditional notion that only β1-ARs support cardiac contractile function has been challenged by recent research demonstrating that cardiac myocytes also express β2-ARs that link to important changes in cardiac contractile function. Although these β2-AR–dependent signals may represent only a relatively minor component of catecholamine responsiveness under normal physiological conditions, β2-ARs assume increased importance as a mechanism for inotropic support in the failing or aged heart, where there is a selective downregulation …

Effects of advanced aging on plasma catecholamine responses to the cold pressor test

Increased basal norepinephrine (NE) concentrations have been demonstrated repeatedly in human aging, but these studies have included almost exclusively “early aging” subjects younger than age 75. We asked if “advanced aging” (over age 80) enhanced the effects of early aging on plasma NE and epinephrine (EPI) concentrations at rest and in response to the cold pressor test (CPT). Eight medically well, cognitively intact advanced aging subjects (84.4 ± 0.9 years), 28 medically well cognitively intact early aging subjects (70.3 ± 1.3 years), and 19 medically well young subjects (25.4 ± 0.9 years) were studied. Both basal NE and the acute NE increase after CPT were significantly higher in advanced aging than in either early aging or young subjects. Plasma EPI concentrations were higher in the advanced aging group than in the other groups and an acute plasma EPI increase after CPT occurred only in the advanced aging group. These results suggest specific effects of advanced aging on both the sympathoneural and sympathoadrenomedullary components of the sympathetic nervous system.

Central corticotropin-releasing hormone receptors modulate hypothalamic–pituitary–adrenocortical and sympathoadrenal activity during stress

The role of brain corticotropin-releasing hormone receptors in modulating hypothalamic–pituitary–adrenal and sympathoadrenal responses to acute immobilization stress was studied in conscious rats under central corticotropin-releasing hormone receptor blockade by intracerebroventicular injection of a peptide corticotropin-releasing hormone receptor antagonist. Blood for catecholamines, adrenocorticotropic hormone and corticosterone levels was collected through vascular catheters, and brains were removed at 3 h for in situ hybridization for tyrosine hydroxylase messenger RNA in the locus coeruleus, and corticotropin-releasing hormone and corticotropin-releasing hormone receptor messenger RNA in the hypothalamic paraventricular nucleus. Central corticotropin-releasing hormone receptor blockade reduced the early increases in plasma epinephrine and dopamine, but not norepinephrine, during stress. Immobilization stress increased tyrosine hydroxylase messenger RNA levels in the locus coeruleus by 36% in controls, but not in corticotropin-releasing hormone antagonist-injected rats. In control rats, corticotropin-releasing hormone messenger RNA and type 1 corticotropin-releasing hormone receptor messenger RNA in the paraventricular nucleus increased after stress ( P<0.01), and these responses were attenuated by central corticotropin-releasing hormone receptor blockade. In contrast, central corticotropin-releasing hormone antagonist potentiated plasma adrenocorticotropic hormone responses, but slightly attenuated plasma corticosterone responses to stress. The inhibition of plasma catecholamine and locus coeruleus tyrosine hydroxylase messenger RNA responses to stress by central corticotropin-releasing hormone receptor blockade supports the notion that central corticotropin-releasing hormone regulates sympathoadrenal responses during stress. The attenuation of stress-induced corticotropin-releasing hormone and corticotropin-releasing hormone receptor messenger RNA responses by central corticotropin-releasing hormone receptor blockade suggests direct or indirect positive feedback effects of corticotropin-releasing hormone receptor ligands on corticotropin-releasing hormone expression, whereas additional mechanisms potentiate adrenocorticotropic hormone responses at the pituitary level. In addition, changes in neural activity by central corticotropin-releasing hormone are likely to modulate adrenocortical responsiveness during stress.

Cardiovascular, autonomic, and plasma catecholamine responses in unilateral and bilateral carotid artery stenosis

OBJECTIVETo determine impairment of baroreceptor afferent activity, which may affect cardiovascular autonomic function in patients with unilateral and bilateral carotid artery stenosis. Comparison was made with normal subjects and hypertensive...

Inpatient experience with remifentanil.

Inpatient experience with remifentanil.

Endurance exercise causes interaction among stress hormones, cytokines, neutrophil dynamics, and muscle damage.

We analyzed adaptation mechanisms regulating systemic inflammatory response of the stressed body by using an experimental challenge of repeated exercise bouts and accompanying muscle inflammation. Eight untrained men bicycled at 90 W for 90 min, 3 days in a row. Exercise induced peripheral neutrophilia with a leftward shift of neutrophil nucleus and neutrophil priming for oxidative activity determined by luminol-dependent chemiluminescence. Plasma growth hormone and interleukin-6 rose significantly after exercise and were closely correlated with the neutrophil responses. Serum creatine kinase and myoglobin levels as muscle damage markers rose after exercise in "delayed onset" and were closely correlated with the preceding neutrophil responses. These exercise-induced responses were strongest on day 1, but the magnitude gradually decreased with progressive daily exercise. In contrast, the magnitude of catecholamine responses to exercise sessions gradually rose, possibly suppressing neutrophil oxidative responses. These results indicate that stress-induced systemic release of bioactive substances may determine neutrophil mobilization and functional status, which then may affect local tissue damage of susceptible organs.

Acid-evoked quantal catecholamine secretion from rat phaeochromocytoma cells and its interaction with hypoxia-evoked secretion.

1. Amperometric recordings using polarized carbon fibre microelectrodes were used to detect exocytosis of catecholamines from rat phaeochromocytoma (PC12) cells in response to a reduction in pHo. 2. Exocytosis was detected at pHo levels of between 7.2 and 6.8. This was probably due to intracellular acidification, since acid-evoked secretion was enhanced by the Na+-H+ exchange blocker ethylisopropylamiloride (30 microM), and was mimicked by sodium propionate (10 mM), which causes selective intracellular acidosis. 3. Acid-evoked exocytosis was abolished by removal of Ca2+o or application of 200 microM Cd2+. It was unaffected by nifedipine, but significantly reduced by either omega-conotoxin GVIA (1 microM) or omega-agatoxin GIVA (200 nM). The two toxins applied together almost completely abolished (> 97 %) acid-evoked secretion. 4. Hypoxia-evoked catecholamine release was potentiated under acidic conditions and suppressed under alkaline conditions in a manner which indicated a greater than additive interaction of these two stimuli. 5. Our results indicate that, like carotid body arterial chemoreceptors, PC12 cells represent model chemoreceptor cells for both hypoxia and acidity and that the release of catecholamines in response to these physiological stimuli is dependent on Ca2+ influx through voltage-gated N- and P/Q-type Ca2+ channels.

Adrenomedullary response to caffeine in prepubertal and pubertal obese subjects.

To investigate whether blunted adrenomedullary responsiveness to stimuli is a primary feature of human obesity in childhood and adolescence Comparison of plasma catecholamine response to caffeine in obese and lean subjects before and after puberty onset. Twelve lean prepubertal subjects (six males and six females), 15 prepubertal obese subjects (seven males and eight females), 12 pubertal lean subjects (six males and six females) and 24 pubertal obese subjects (12 males and 12 females) Plasma levels of Luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17beta-estradiol and testosterone were used to validate Tanner score. Systolic and diastolic blood pressure, pulse rate and plasma catecholamines before and after caffeine administration (4 mg/kg of ideal body weight). Caffeine administration significantly stimulated adrenaline release in all subjects studied. The incremental area of adrenaline response to caffeine, analysed by multiple comparison test, was lower in pubertal obese subjects with respect to other groups. At variance with what is observed in adulthood obesity, prepubertal obese subjects show an intact adrenomedullary response to caffeine.

Neuronal control of catecholamine secretion from chromaffin cells in the rainbow trout (Oncorhynchus mykiss).

The goal of the present investigation was to assess the relative involvement of nicotinic and muscarinic cholinergic receptors in the neuronal control of catecholamine secretion from the chromaffin tissue of rainbow trout (Oncorhynchus mykiss). This was accomplished by first developing and validating a nerve-stimulating technique able specifically to activate the nerve fibres innervating the chromaffin cells in order to elicit secretion of catecholamines. Using an in situ saline-perfused posterior cardinal vein preparation, it was demonstrated that whole-body field stimulation caused specific voltage-dependent neuronal stimulation of adrenaline and noradrenaline secretion. The contribution of non-specific depolarization was negligible. Several experimental results confirmed the specificity of the field stimulation technique. First, pre-treatment with neostigmine (an anticholinesterase) prolonged and more than doubled the amount of adrenaline secreted in response to electrical stimulation. Second, pre-treatment with the nicotinic receptor antagonist hexamethonium inhibited the electrically evoked secretion of adrenaline and noradrenaline. Third, perfusion with Na+-free saline or removal of the spinal cord abolished secretion of both catecholamines in response to the electrical stimulus. By using the field stimulation technique, this study is the first to demonstrate conclusively a role for muscarinic receptors in catecholamine secretion from trout chromaffin cells. Specifically, muscarinic cholinergic stimulation enhances nicotinic-evoked secretion of catecholamines and, under intense stimulation, may directly cause secretion. The results of the present study suggest the presence of muscarinic receptors on rainbow trout chromaffin cells with a functional role in the cholinergic control of catecholamine secretion.

Between 21 and 34 years of age, aging alters the catecholamine responses to supramaximal exercise in endurance trained athletes.

The purpose of this study was to determine the effect of aging and training on the adrenaline (A) and noradrenaline (NA) responses during the Wingate-test in three age groups of subjects: 21 year old untrained subjects (21U), 21 year old endurance trained (21T) (national elite runners), 34 year old endurance trained (34T) (national elite runners). Performances during the test were judged using the usual parameters of peak power (Wmax) and mean power (W) expressed in absolute or relative values. A and NA responses were measured at rest (A0 and NA0) immediately at the end of the exercise (Amax and NAmax) and after 5 minutes recovery (A5 and NA5). Plasma maximal lactate (La(max)) was determined 3 minutes after the end of the exercise. Wmax, W and La(max) were always significantly lower in 34T compared to 21T and 21U. The catecholamine responses were similar in 21T and 21U. Inversely, a significantly lower value of Amax was observed in 34T (2.01 +/- 0.5 nmol x l(-1)) compared to 21U (3.62 +/- 0.3 nmol x l(-1)) associated with a significantly higher value of NA(max) in 34T versus 21T and 21U. Thus, the Amax/NA(max) ratio was found to be significantly lower in the older subjects versus both 21T and 21U. All these findings indicated that endurance training did not affect the sympathoadrenergic responses to a supramaximal exercise and suggested that only one decade may reduce the capacity of the medulla to secrete adrenaline and therefore the adrenal medulla responsiveness to the sympathetic nervous activity.

Yohimbine use in a natural setting: effects on posttraumatic stress disorder

Background: Numerous laboratory-based studies have shown that chronic posttraumatic stress disorder (PTSD) is associated with alterations in catecholamines. In a recent neuroendocrine challenge study, IV yohimbine caused exaggerated subjective, behavioral, cardiovascular and catecholamine responses among combat veterans with PTSD compared to healthy controls. Yohimbine is an alpha-2-adrenergic receptor antagonist that activates noradrenergic neurons. Methods: This report describes the experience of 4 individuals with PTSD who took over-the-counter oral yohimbine that they had purchased from a health food store or pharmacy. Results: All 4 subjects experienced a marked exacerbation of anxiety/panic and PTSD-specific symptoms immediately after ingesting yohimbine in a natural setting. Conclusions: The response in these individuals closely resembled the response observed after IV yohimbine in combat veterans with PTSD. The present cases occurred in a natural setting and thus complement laboratory-based findings. The authors caution against the recreational or medical use of yohimbine in individuals who have PTSD.

Comparison of the effects of four ACE inhibitors on sympathetic reactivity to cold pressor test in essential hypertensive patients

Background. We compared the effects of four different structural angiotensin-converting enzyme (ACE) inhibitors on the hemodynamic profile and catecholamine response to the cold pressor test (CPT) in hypertensive patients. Methods. We studied 44 patients with mild to moderate essential hypertension. The patients were divided into four groups according to the ACE inhibitor [enalapril (E), fosinopril (F), captopril (C), or ramipril (R)]. They were given for 8 weeks. Sympathetic reactivity was evaluated by a CPT at baseline and at the end of therapy. Blood pressure (BP), heart rate (HR), and plasma norepinephrine (NE, pg ml−1) were measured at the times 0, 2, 4, 6, 8, 10, and 15 min. The delta (subtracting the basal values from the min 2 values) and the area under the curve (AUC) of the response during the CPT were studied. Results. The rise in diastolic blood pressure (DBP) (AUC) during the cold stimulus was significantly attenuated by all inhibitors studied (P<0.01): E, 17±22 to 0±20; F, 23±41 to −4±40; C, 34±33 to 7±28; R, 32±28 to −1±25. Drug therapy also blunted the response of HR to cold stress (delta HR, bpm): E, 2±2 to 0±2, P<0.05; F, 2±2 to 0±2, P<0.05; C, 3±3 to −1±3, P<0.01; R, 2±4 to −2±3, P<0.05. The rise in plasma NE (AUC) during CPT was decreased by all ACE inhibitors: E, 198±405 to 24±148, P<0.05; F, 353±436 to 51±412, P<0.05; C, 315±318 to 124±516, P<0.05; R, 677±398 to 251±307, P<0.01. Conclusions. The results in our study suggest that the blunting effects of ACE inhibitors on adrenergic tone seem to be class-dependent.

Effects of caffeine and promazine hydrochloride on plasma catecholamines in thoroughbreds at rest and during treadmill exercise.

Our aim was to investigate plasma catecholamine responses to so-called 'doping' drugs and exercise in Thoroughbreds. Plasma adrenaline (Ad) and noradrenaline (NA) were determined after the administration of caffeine and promazine hydrochloride (PRZ) using a high performance liquid chromatographic method. Caffeine or PRZ was administered i.m. to Thoroughbreds and its effects on plasma catecholamines at rest and during exercise were compared with the saline control. The treadmill exercise was performed 1 h after administration. A dose of 5.0 mg/kg bwt caffeine was found to significantly increase both plasma Ad and NA levels but this was not the case for the 2.5 mg/kg bwt dose and their peak levels at 1.5 h were about 3 and 2.5 times as compared with the control values at 1.5 h (Ad: mean +/- s.e. 21.2 +/- 2.8 pg/ml, NA: 55.5 +/- 4.1 pg/ml), respectively. Both 1.0 and 1.5 mg/kg bwt PRZ doses reduced the plasma Ad to below the detection limit (10 pg/ml) and significantly reduced the plasma NA. The 2.5 mg/kg bwt caffeine dose significantly increased plasma Ad and NA during exercise and approximately doubled their maximal values as compared with the saline control (Ad: mean +/- s.e. 12.328 +/- 4.733 ng/ml, NA: 9.997 +/- 4.146 ng/ml). The 1.5 mg/kg bwt PRZ dose decreased the plasma Ad during exercise but the effect was not significant. On the other hand, PRZ significantly increased the plasma NA as compared with the saline control. In conclusion, the present study demonstrates that the plasma catecholamine responses to caffeine and PRZ were modified by exercise. It is probable that the modification may be related to exercise-induced activation of the sympathetico-adrenal axis.

Plasma adrenocorticotropin, cortisol and catecholamines response to various exercises.

The responses of plasma adrenocorticotropin (ACTH), cortisol, noradrenaline and adrenaline in 5 Thoroughbred horses to an incremental exercise and 2 relative workload exercises, at 105 and 80% maximal oxygen consumption (VO2max), on a treadmill were examined. These hormone concentrations increased (P < 0.05) with each exercise and the maximal plasma concentrations of ACTH, cortisol were observed between 5 and 30 min after the end of the exercise, while maximal catecholamine concentrations occurred just at exhaustion time. The plasma ACTH, noradrenaline and adrenaline responses during exercise were more sensitive to the intensity of exercise than that of cortisol and showed a significant correlation with blood lactate concentrations (r = 0.605, P < 0.001 for ACTH; r = 0.718, P < 0.001 for noradrenaline; r = 0.738, P < 0.001 for adrenaline). The plasma cortisol response appeared to be connected with the duration of exercise (r = 0.71, P < 0.05). The recovery of these hormones was related to the exercise styles. These results suggest that the autonomic nervous system and the pituitary-adrenal axis of the horse are efficiently stimulated by various treadmill exercises, and these hormones may be used in the evaluation of exercise-induced stress.

Functional involvement of angiotensin AT2receptor in adrenal catecholamine secretion in vivo

The aim of the present study was to analyse modulations of adrenal catecholamine secretion from the adrenal gland of anesthetized dogs in response to locally administered angiotensin II (AngII) in the presence of either PD 123319 or CGP 42112, both of which are highly specific and selective ligands to angiotensin AT2 receptor. Plasma concentrations of epinephrine and norepinephrine in adrenal venous and aortic blood were quantified by a high performance liquid chromatography coupled with electrochemical detection (HPLC-EC) method. Adrenal venous blood flow was measured by gravimetry. Local administration of AngII (0.05 microg, 0.1 microM) to the left adrenal gland increased adrenal gland catecholamine output more than 30 times that found in nonstimulated states. Administration of either PD 123319 (0.085 microg (0.23 microM) to 8.5 microg (23 microM)) or CGP 42112 (0.005 microg (0.01 microM) to 5 microg (10 microM)) did not affect the basal catecholamine output significantly. The increase in adrenal catecholamine output in response to AngII was inhibited by approximately 80% following the largest dose of PD 123319. CGP 42112 significantly attenuated the catecholamine response to AngII by approximately 70%. PD 123319 and CGP 42112 were devoid of any agonist actions with respect to catecholamine output by the adrenal gland in vivo. Furthermore, both PD 123319 and CGP 42112 inhibited the increase in adrenal catecholamine secretion induced by local administration of AngII. The present study suggests that AT2 receptors play a role in mediating catecholamine secretion by the adrenal medulla in response to AngII receptor agonist administration in vivo.

Disease Activity Related Catecholamine Response of Lymphocytes from Patients with Rheumatoid Arthritis

In patients with chronic rheumatic diseases, a decreased density of beta 2-adrenergic receptors (beta 2R) on peripheral blood mononuclear cells (PBMC) could be demonstrated negatively correlating with various disease activity parameters. The aim of the present study was to determine the impact of this decrease on catecholamine response of PBMC from patients with rheumatoid arthritis (RA) in vitro. PBMC from 17 patients with RA and 6 healthy blood donors (HD) were investigated. The effects of epinephrine (E) and norepinephrine (NE) on PBMC proliferation were studied using cells activated with phytohemagglutinin (PHA) and monoclonal anti-CD3-antibodies (OKT3), respectively. The results revealed that lymphocytes of patients with RA showed a significantly reduced influence of catecholamines on PBMC function. In RA patients with high disease activity only, a shift to alpha 1-adrenergic-mediated catecholamine effects upon PBMC reactivity could be observed. The study demonstrates the intricate relationship between PBMC reactivity and catecholamine effects that is mediated via alpha- and beta-adrenergic receptors due to disease activity. In this respect the altered catecholamine response of PBMC from patients with RA may contribute to the pathogenic process of RA.