Epinephrine Output Research Articles

A 4-session written emotional disclosure intervention lowers 6-month sympathoadrenal urinary output in persons living with HIV

ObjectiveWe previously reported that a brief guided written emotional disclosure (WED) intervention resulted in significant reductions in post-traumatic stress disorder (PTSD) symptomology in women, but not men, living with HIV. Levels of 24-hour urinary output of epinephrine (E) and norepinephrine (NE) are shown to be elevated in persons diagnosed with PTSD. The current study tested whether there was an effect for the 4-week WED intervention on 6-month change in urinary E and NE output amongst persons living with HIV. MethodFourteen women and 11 men living with HIV randomized to four 30-min expressive writing sessions of either trauma writing or daily events writing in the parent trial were included based upon collection of urine specimens at baseline, 1-, and 6-months after the intervention. Total volume (µg) and concentration (µg/ml) of urinary E and NE were derived from the specimens as study outcomes. ResultsFour repeated measures analyses of covariance (ANCOVA) were performed to evaluate study outcomes using trauma- versus daily-writing as the between-subject factors and collection time point as the within-subject factor, controlling for age and sex. A group x time interaction was observed wherein the trauma writing treatment group showed a significantly greater decrease in total urinary output, F(2, 46) = 4.03, p = .03, and concentration, F(2, 46) = 4.74, p = .01 of epinepherine. Post-hoc analyses revealed the interaction effect for the total, F(2, 22) = 4.82, p = .03, and concentration, F(2, 22) = 7.57, p = .005, of urinary E output over 6-months was significant for women. Interactions were not observed in urinary NE output. ConclusionsSignificant reductions in the total output and concentration of urinary E were found up to 6-months following initiation of a 4-session guided written emotional disclosure intervention. Profiles of sympathoadrenal activity and response to expressive writing differ between men and women living with HIV. Futher research is need to characterize the putative pathways linking sympathoadrenal response to upstream neurobiological function and downstream inflammatory-immune status in women living with HIV and PTSD.

Overnight/first-morning urine free metanephrines and methoxytyramine for diagnosis of pheochromocytoma and paraganglioma: is this an option?

Sympathoadrenal activity is decreased during overnight rest. This study assessed whether urinary-free normetanephrine, metanephrine and methoxytyramine in overnight/first-morning urine collections might offer an alternative to measurements in 24-h collections or plasma for diagnosis of pheochromocytoma and paraganglioma (PPGL). Prospective multicenter cross-sectional diagnostic study involving 706 patients tested for PPGL, in whom tumors were confirmed in 79 and excluded in 627 after follow-up. Another 335 age- and sex-matched volunteers were included for reference purposes. Catecholamines and their free O-methylated metabolites were measured in 24-h collections divided according to waking and sleeping hours and normalized to creatinine. Plasma metabolites from blood sampled after supine rest were measured for comparison. Urinary outputs of norepinephrine, normetanephrine, epinephrine and metanephrine in the reference population were respectively 50 (48-52)%, 35 (32-37)%, 76 (74-78)% and 15 (12-17)% lower following overnight than daytime collections. Patients in whom PPGLs were excluded showed 28 (26-30)% and 6 (3-9)% day-to-night falls in normetanephrine and metanephrine, while patients with PPGLs showed no significant day-to-night falls in metabolites. Urinary methoxytyramine was consistently unchanged from day to night. According to receiver-operating characteristic curves, diagnostic accuracy of metabolite measurements in overnight/first-morning urine samples did not differ from measurements in 24-h urine collections, but was lower for both than for plasma. Using optimized reference intervals, diagnostic specificity was higher for overnight than daytime collections at similar sensitivities. Measurements of urinary-free catecholamine metabolites in first-morning/overnight urine collections offer an alternative for diagnosis of PPGL to 24-h collections but remain less accurate than plasma measurements.

The effects of age and ethnicity on the circadian variation of catecholamines and cortisol in employed women

BackgroundWomen employed outside the home in urban settings must adapt to changing circadian microenvironments. The pattern and extent of vasoactive hormone responses to these changes may depend upon age and ethnic background. The purpose of this study was to evaluate the effects of age and ethnicity on the circadian variation of urinary norepinephrine, epinephrine, and cortisol excretion across work, home and sleep microenvironments.MethodsThe subjects of the study were 95 women (38 European-American, age = 35.4 ± 7.4; 28 African-American, age = 33.4 ± 7.9; 12 Asian-American, age = 36.7 ± 9.3 and 17 Hispanic-American age = 31.6 ± 10.9) employed as secretaries, lab technicians or office supervisors in New York City. Variation in the hormones across the microenvironments was evaluated using repeated measures ANCOVA with age group (18–29.9; 30–39.9; 40–49.9) and ethnicity as fixed factors.ResultsThe results show that for norepinephrine and epinephrine, work excretion rates are substantially higher than sleep rates (p < .001), and for epinephrine home rates were higher than sleep rates (p < .001). Work and sleep cortisol excretion rates were also significantly higher than the rate at home, consistent with cortisol’s circadian rhythm. (p < .002). Women in their twenties had substantially lower norepinephrine excretion rates than women over 30 (p < .04). There were also ethnic differences in norepinephrine (p < .04) and epinephrine (p = .11) output with Asian-American women having the lowest and African-American women having the highest rates. This variation is likely related to the ethnic variation in weight. There was no significant variation in cortisol excretion with age or ethnicity.ConclusionThe circadian rates of norepinephrine excretion differ by age and that of both catecholamines differ by ethnicity among women working outside the home. It is speculated that the age variation in norepinephrine may contribute to the development of vasomotor symptoms.

Integrative Genetic Characterization and Phenotype Correlations in Pheochromocytoma and Paraganglioma Tumours

BackgroundAbout 60% of Pheochromocytoma (PCC) and Paraganglioma (PGL) patients have either germline or somatic mutations in one of the 12 proposed disease causing genes; SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, EPAS1, RET, NF1, TMEM127, MAX and H-RAS. Selective screening for germline mutations is routinely performed in clinical management of these diseases. Testing for somatic alterations is not performed on a regular basis because of limitations in interpreting the results.AimThe purpose of the study was to investigate genetic events and phenotype correlations in a large cohort of PCC and PGL tumours.MethodsA total of 101 tumours from 89 patients with PCC and PGL were re-sequenced for a panel of 10 disease causing genes using automated Sanger sequencing. Selected samples were analysed with Multiplex Ligation-dependent Probe Amplification and/or SNParray.ResultsPathogenic genetic variants were found in tumours from 33 individual patients (37%), 14 (16%) were discovered in constitutional DNA and 16 (18%) were confirmed as somatic. Loss of heterozygosity (LOH) was observed in 1/1 SDHB, 11/11 VHL and 3/3 NF1-associated tumours. In patients with somatic mutations there were no recurrences in contrast to carriers of germline mutations (P = 0.022). SDHx/VHL/EPAS1 associated cases had higher norepinephrine output (P = 0.03) and lower epinephrine output (P<0.001) compared to RET/NF1/H-RAS cases.ConclusionSomatic mutations are frequent events in PCC and PGL tumours. Tumour genotype may be further investigated as prognostic factors in these diseases. Growing evidence suggest that analysis of tumour DNA could have an impact on the management of these patients.

DIFFERENTIAL EFFECTS OF PHOTOPHASE IRRADIANCE ON METABOLIC AND URINARY STRESS HORMONE CONCENTRATIONS IN BLIND AND SIGHTED RODENTS

The effects of different photophase irradiance levels on the daily rhythms of energy expenditure (DEE, calculated from oxygen consumption, VO2) and urinary metabolites of stress hormones in sighted (Microtus socialis) and blind (Spalax ehrenbergi) rodents were compared. Five groups of each species were exposed to different irradiance levels (73, 147, 293, 366, and 498 μW/cm2) under short photoperiod (8L:16D) condition with constant ambient temperature 25 ± 2°C for 21 days before assessments. As light intensity increased from 73 μW/cm2, both species reduced DEE, especially among M. socialis. Cosinor analysis revealed significant ultradian rhythms in VO2 of M. socialis with period length being inversely related to irradiance level. Conversely, in S. ehrenbergi, robust 24 h VO2 rhythms were detected at all irradiances. In M. socialis, significant 24 h rhythms in urinary output of adrenaline were detected only at 293 μW/cm2, whereas for cortisol, unambiguous rhythms were detected at 73 and 147 μW/cm2. Distinct adrenaline daily rhythms of S. ehrenbergi were observed at 73 and 293 μW/cm2, whereas this species exhibited significant rhythms in cortisol at 147 and 293 μW/cm2. Changes in photophase irradiance levels affected stress hormone concentrations in a dose-dependent manner. There were significant negative and positive correlations of M. socialis and S. ehrenbergi stress hormones, respectively, with increasing irradiance. Our results indicate photophase light intensity is another environmental factor that can significantly affect entrainment of mammalian daily rhythms. Both low and high irradiance conditions can trigger stress responses, depending on the species' natural habitat. (Author correspondence: zubidat3@013.net.il)

Centrally evoked increase in adrenal sympathetic outflow elicits immediate secretion of adrenaline in anaesthetized rats

To examine whether feedforward control by central command activates preganglionic adrenal sympathetic nerve activity (AdSNA) and releases catecholamines from the adrenal medulla, we investigated the effects of electrical stimulation of the hypothalamic locomotor region on preganglionic AdSNA and secretion rate of adrenal catecholamines in anaesthetized rats. Pre- or postganglionic AdSNA was verified by temporary sympathetic ganglionic blockade with trimethaphan. Adrenal venous blood was collected every 30 s to determine adrenal catecholamine output and blood flow. Hypothalamic stimulation for 30 s (50 Hz, 100-200 microA) induced rapid activation of preganglionic AdSNA by 83-181% depending on current intensity, which was followed by an immediate increase of 123-233% in adrenal adrenaline output. Hypothalamic stimulation also increased postganglionic AdSNA by 42-113% and renal sympathetic nerve activity by 94-171%. Hypothalamic stimulation induced preferential secretion of adrenal adrenaline compared with noradrenaline, because the ratio of adrenaline to noradrenaline increased greatly during hypothalamic stimulation. As soon as the hypothalamic stimulation was terminated, preganglionic AdSNA returned to the prestimulation level in a few seconds, and the elevated catecholamine output decayed within 30-60 s. Adrenal blood flow and vascular resistance were not affected or slightly decreased by hypothalamic stimulation. Thus, it is likely that feedforward control of catecholamine secretion from the adrenal medulla plays a role in conducting rapid hormonal control of the cardiovascular system at the beginning of exercise.

Effects of the GABA-A receptor agonist and antagonist on the in vitro release of hypothalamic catecholamines: apparent parallelism between these effects and the LHRH secretion in adult male rats.

GABA (gamma-aminobutyric acid) has a well-known inhibitory effect on the luteinizing hormone-releasing hormone (LHRH) secretion. In order to evaluate the contribution of the catecholaminergic neurotransmitters on the inhibitory effect produced by GABA on the LHRH release, we measured in adult male rats the in vitro hypothalamic output of LHRH, epinephrine (E), norepinephrine (NE) and dopamine (DA); after the administration of, either muscimol 1 microM (GABA-A agonist), and/or 1 microM bicuculline (GABA-A antagonist). The following results were obtained: muscimol inhibited LHRH secretion, and this effect was accompanied by a decrease of NE, E and DA output. The opposite effects were observed after the addition of bicuculline, i.e, stimulation of LHRH, NE, E and DA release. In conclusion, our results show that, in the adult male rats, GABA has an inhibitory effect on the in vitro release of LHRH, acting on the GABA-A receptor. This effect on LHRH secretion might be exerted directly, or indirectly, by altering the release of either NE,E, and/or DA.

Low- versus high-baseline epinephrine output shapes opposite innate cytokine profiles: presence of Lewis- and Fischer-like neurohormonal immune phenotypes in humans?

Immunogenetic mechanisms operating within the immune system are known to influence cytokine profiles and disease susceptibility. Yet the role of the individual's neurohormonal background in these processes remains undefined. Hormonal imbalances are documented in immune-related diseases, but it is unclear whether this represents a secondary phenomenon or a primary "defect" related to specific neurohormonal immune phenotype(s). We report that in a large subpopulation of healthy humans the baseline epinephrine output (but not cortisol and sex steroid hormones) correlated inversely with proinflammatory and positively with anti-inflammatory cytokine production. Thus, low vs high epinephrine excretors had a 2- to 5-fold higher TNF-alpha and IL-12 production but 2-fold lower IL-10 production induced by LPS ex vivo. In alternative settings, we found low baseline levels and profoundly blunted stress-induced epinephrine responses but high TNF-alpha levels in Lewis vs Fischer inbred rats. Additionally, isoproterenol, a beta adrenoreceptor agonist suppressed LPS-induced TNF-alpha production, with more pronounced effect in Lewis than in Fischer rats. In human monocytes, epinephrine and the beta(2) adrenoreceptor agonist fenoterol potently inhibited LPS-induced TNF-alpha and IL-12, but stimulated IL-10 production. The order of potency for hormones able to inhibit IL-12 production ex vivo was: epinephrine > norepinephrine > or = 1,25-(OH)(2) vitamin D(3) > hydrocortisone. This indicates that baseline epinephrine conditions cytokine responsiveness and through this mechanism intrinsic hypo- or hyperactive adrenal medullas in some individuals may shape opposite cytokine profiles. Since Lewis and Fischer rats have opposite susceptibility to experimental immunological diseases, this suggests that the parallel human phenotypes could be linked to differing responsiveness and susceptibility to infections and immune/inflammatory-related conditions.

Catecholamine release and excretion in rats with immunologically induced preganglionic sympathectomy.

Plasma and urinary catecholamines were quantified to assess global sympathoadrenal function in rats with preganglionic lesions caused by antibodies to acetylcholinesterase (AChE). Rats were given intravenous injections of normal mouse IgG or murine monoclonal anti-acetylcholinesterase IgG (1.5 mg). Five or 16 days afterward, basal blood samples were taken through indwelling arterial cannulate. A few hours later, the rats were immobilized for 10 min in padded restrainers, and another blood sample was drawn. HPLC determinations showed low basal levels of norepinephrine and epinephrine (< 0.2 ng/ml in all rat plasma samples). In control rats, immobilization stress increased levels of plasma catecholamines up to 35-fold. In rats tested 5 days after injection of antibody, the norepinephrine response was much smaller (15% of control), and the epinephrine response was nearly abolished (5% of control). There was some recovery at 16 days after antibody treatment, but stress-induced catecholamine release was still markedly impaired. Reduced stress-induced release was not accompanied by major changes in tissue epinephrine or norepinephrine (heart, spleen, adrenal glands, and brain), although adrenal dopamine content dropped by 60%. Urinary excretion was studied in parallel experiments to gain insight into the effects of AChE antibodies on basal sympathoadrenal activity. Epinephrine, norepinephrine, dopamine, and selected metabolites were quantified in 24-h urine samples collected at frequent intervals for 30 days after antibody injection. No statistically significant changes were detected in the urinary output of dopamine, 3-methoxytyramine, normetanephrine, or 3-methoxy-4-hydroxyphenylglycol. On the other hand, epinephrine and norepinephrine output increased sharply at the time of antibody injection and then fell significantly below control levels. Norepinephrine output returned to normal after 2 weeks, but epinephrine output remained depressed. These results are consistent with previous evidence of widespread and persistent antibody-mediated damage to the preganglionic sympathetic system.

Findings from a naturalistic drug utilization observation phase IV study: Subjective well-being, quality of life, and global functioning in schizophrenic patients treated with olanzapine

Psychoendocrine and behavioural effects elicited by viewing an exciting and partly violent movie were studied in 12-year-old boys (n = 42). The boys were divided into three groups. Group A (n = 13) consisted of boys scoring below the median value on the Sennton neurotic scale for vegetative anxiety symptoms. Group B (n = 13) consisted of boys scoring above the median value on the Sennton neurotic scale. None of these boys had ever visited a psychiatric treatment centre, and they all came from the same school. A third group, Group C (n = 16), consisted of boys who, at least once, had visited an out-patient clinic at a child psychiatric treatment centre for neurotic problems. These boys attended different schools in the hospital catchment area. Group C had the same mean score on the Sennton neurotic scale as did Group B. By having two groups of boys scoring both high on the Sennton neurotic scale, one of which knew the other boys and one that did not, we were able to study possible effects of social support on psychobiologic reactions in neurotic boys. The boys' reactions to the movie were assessed by: (1) self-ratings; (2) direct observations of the boys by a team of trained child psychologists; and (3) by analysis of urinary output of adrenaline, noradrenaline and cortisol. Group B rated their experience the strongest, viewing the movie, while Groups A and C rated themselves as rather unaffected by it. Group C was rated less verbally active, both during the control and the film periods, than were the other two groups. Group A was most motorically active during the film period.There were no significant differences during the control period in endocrine variables. During the film period Group C excerted significantly more noradrenaline than did Group A, and significantly more noradrenaline than did Group B. Intra-group differences in response to the movie were also assessed. Adrenaline excretion increased significantly only in Group C during the movie, compared with the control period. Furthermore, excretion of noradrenaline decreased significantly during the film period in Groups A and B. The A and B groups preferred to review scenes representing danger, while Group C preferred scenes representing security. It is suggested that psychosocial factors, e.g. novelty to the environment and lack of friends, caused the differences between Group C and the other two groups. Group C, which scored the same as Group B on Sennton neurotic scale, did not have access to social support in the form of friends during the movie. They were left alone with their anxiety, with little ability to express it in a group of unknown boys. Group B appeared to have coped in a more ‘open way’, expressing their emotions during the film period, possibly explaining this group's lower level of physiological arousal. The psychological vulnerability in Group C is further stressed by this group's desire to review scenes depicting security. It suggested that access to social support, here operationally defined as being together with friends, is an important intervening variable in predicting psychobiological effects of viewing exciting and violent motion pictures.

No correlation between phaeochromocytoma catecholamine secretion and granule ultrastructure.

It is uncertain whether biochemical markers of catecholamine secretion in patients with phaeochromocytoma correlate with tumour ultrastructure granule morphology. Fifteen patients with an adrenal phaeochromocytoma (n=13) or paraganglioma (n=2) (three men, 12 women; age 17-79 years) were studied. Catecholamine secretion was estimated by measuring urinary levels of free noradrenaline, adrenaline and dopamine. The number and type of secretory granules were evaluated by two independent observers on electron micrographs (area analysed approximately 70 microm2). Large round or elongated medium-density granules were adrenaline-type granules, whereas electron-dense granules lying in a vacuole were of noradrenaline type. No correlation was found between noradrenaline output and the number or percentage of noradrenaline-type granules, although tumours with normal noradrenaline output had only a minority of this type of granule (less than 25 per cent). Adrenaline-type granules were predominant (77 per cent of 163 granules) in a tumour secreting only adrenaline, but the proportion of adrenaline-type granules in six tumours with normal adrenaline output varied significantly (range 7-89 per cent). It was not possible to evaluate the granule type associated with dopamine secretion because one tumour secreting 14900 nmol dopamine and 1570 nmol adrenaline daily had a predominance of noradrenaline-type granules (63 per cent of 132 granules) and two dopamine-secreting tumours (5500 and 4250 nmol per day respectively) had 93 and 13 per cent noradrenaline-type granules. The lack of correlation between hormone output and granularity suggests that other factors determine secretory patterns in these tumours.

Clonidine as a drug for intravenous conscious sedation.

Clonidine, an alpha(2)-adrenoceptor agonist, was introduced to clinical practice in the 1960s because of its antihypertensive effect. It has several beneficial actions during the perioperative period, particularly for medically compromised patients. The objective of this study was to evaluate the effects of clonidine as a drug for intravenous conscious sedation. We assessed the effects of intravenous clonidine on the hemodynamic and sympathoadrenergic responses to nociceptive stimuli and we evaluated its sedative and analgesic effects. Twenty-five volunteers aged between 23 and 25 years were included in this study. They received clonidine intravenously at 2 microg/kg. Constant-current, square-wave stimuli were delivered as nociceptive stimuli to the median nerve of the arm. We measured blood pressure, heart rate, cardiac output, and plasma concentrations of noradrenaline, adrenaline, and cortisol. The sedative and analgesic effects were measured by visual analogue scales. Changes in heart rate and blood pressure were not significantly different between the clonidine and control groups. Cardiac output tended to decrease after clonidine administration. Clonidine exerted its greatest sedative effect 30 min after injection. Noradrenaline concentration reached its nadir 15 min after clonidine administration. The time course of adrenaline concentrations was similar to that of noradrenaline. The plasma concentration of cortisol decreased in both groups. The most common adverse effect was dry mouth. In conclusion, intravenous clonidine, at a dose of 2 microg/kg, did not induce significant bradycardia, hypotension, or severe side effects in the healthy volunteer. It attenuated the adrenergic response to electrical stimulation. The results suggested that clonidine is a useful drug for intravenous sedation.

Role of K + channels in the PACAP-induced catecholamine secretion from the rat adrenal gland

We eluciated whether K + channels modulate adrenal catecholamine secretion induced by pituitary adenylate cyclase-activating polypeptide (PACAP) in the isolated perfused rat adrenal gland. PACAP (100 nM) increased adrenal epinephrine output. The PACAP-induced responses were enhanced by treatment with apamin (10–100 nM) in a concentration-dependent manner. In the presence of nifedipine (3 μM), apamin (1 μM) did not enhance the PACAP-induced responses. Charybdotoxin (1–100 nM) had little influence on the PACAP-induced responses. These results suggest that small-conductance Ca 2+-activated K + channels interfere with L-type voltage-dependent Ca 2+ channels to counteract the PACAP-induced adrenal catecholamine secretion.

Interaction of SK(Ca) channels and L-type Ca(2+) channels in catecholamine secretion in the rat adrenal gland.

We elucidated the interaction of small-conductance Ca(2+)-activated K(+) (SK(Ca)) channels and L-type Ca(2+) channels in muscarinic receptor-mediated control of catecholamine secretion in the isolated perfused rat adrenal gland. The muscarinic agonist methacholine (10-300 microM) produced concentration-dependent increases in adrenal output of epinephrine and norepinephrine. The SK(Ca) channel blocker apamin (1 microM) enhanced the methacholine-induced catecholamine responses. The facilitatory effect of apamin on the methacholine-induced catecholamine responses was not observed during treatment with the L-type Ca(2+) channel blocker nifedipine (3 microM) or Ca(2+)-free solution. Nifedipine did not affect the methacholine-induced catecholamine responses, but it inhibited the responses during treatment with apamin. The L-type Ca(2+) channel activator Bay k 8644 (1 microM) enhanced the methacholine-induced catecholamine responses, whereas the enhancement of the methacholine-induced epinephrine and norepinephrine responses were prevented and attenuated by apamin, respectively. These results suggest that SK(Ca) channels are activated by muscarinic receptor stimulation, which inhibits the opening of L-type Ca(2+) channels and thereby attenuates adrenal catecholamine secretion.

Role of calcium channels in catecholamine secretion in the rat adrenal gland.

1. We elucidated the contribution of voltage-dependent Ca2+ channels to cholinergic control of catecholamine secretion in the isolated perfused rat adrenal gland. 2. Nifedipine (0.3-3 microM) inhibited increases in noradrenaline output induced by transmural electrical stimulation (1-10 Hz) and acetylcholine (6-200 microM), whereas it only slightly inhibited the adrenaline output responses. Nifedipine also inhibited the catecholamine output response induced by 1, 1-dimethyl-4-phenyl-piperazinium (DMPP; 5-40 microM) but not by methacholine (10-300 microM). 3. omega-Conotoxin MVIIC (10-1000 nM) inhibited the catecholamine output responses induced by electrical stimulation but not by acetylcholine, DMPP and methacholine. 4. omega-Conotoxin GVIA (50-500 nM) had no inhibitory effect on the catecholamine output responses. 5. These results suggest that L-type Ca2+ channels are responsible for adrenal catecholamine secretion mediated by nicotinic receptors but not by muscarinic receptors, and that their contribution to noradrenaline secretion may be greater than that to adrenaline secretion. P/Q-type Ca2+ channels may control the secretion at a presynaptic site.

Urinary catecholamine excretion in relation to renal function.

The urinary excretions of the free catecholamines noradrenaline, adrenaline and dopamine were measured in 50 patients (33 men and 17 women) with chronic renal failure. Stability studies showed that the catecholamines were stable in unacidified urine as long as the pH was not greater than 7.5 and the urine was acidified within 2-3 h of collection. The outputs of noradrenaline and dopamine correlated positively with creatinine clearance and in patients with clearances above 40 mL/min were similar to those in healthy volunteers (n = 20). However, adrenaline output was not correlated with creatinine clearance although it was lower in patients with renal failure compared with healthy volunteers. The urinary free catecholamine output during the first 10 days after a renal transplant was significantly less than normal, presumably because renal function was still impaired. However, in patients treated with cyclosporin A (CyA) combined with prednisolone the catecholamine excretion was lower compared with those treated with CyA and azathioprine. Impairment in renal function can have a marked effect on the output of free catecholamines and must be borne in mind when interpreting values that may have pathological significance.

Gender Differences in Diurnal Growth Hormone and Epinephrine Values in Young Adults during Ambulation

In the present study, the impact of gender, oral contraceptives, and ambulation on serum growth hormone (GH) and urinary catecholamines was examined in healthy young adults. Twenty-one medical student volunteers--7 men, 7 women, and 7 women taking oral contraceptives--were investigated. Serum samples were drawn every second hour during a 24-h period. At 0800 the first morning, serum samples were drawn while subjects were in the ambulatory state; the next morning, serum samples were drawn at 0800 while the subjects were still resting in bed. During the daytime, GH concentrations were sevenfold higher in the women than in the men, a difference larger than described previously. During the night, there was no gender difference. In the morning, ambulatory GH concentrations were 28-fold higher in the women than in the men, whereas supine GH concentrations were only 4.6-fold higher in the women than in the men. Daytime urinary output of epinephrine was lower in the women than in the men, whereas there was no difference at night. Women using estrogen-containing oral contraceptives had lower epinephrine and higher GH values than women not taking oral contraceptives. In women, morning GH concentrations were higher in the ambulatory than in the resting state, whereas they were lower in the ambulatory state than in the resting state in men. The secretion of GH and epinephrine is gender-dependent and differs during the daytime in a reciprocal manner, with higher GH and lower epinephrine in women than in men. Oral contraceptives appear to further increase such differences. It seems likely that the data reflect a gender difference in the utilization of substrates for energy production.

P–308 - Appearance of nicotine-sensitivity on adrenaline output from adrenals by starvation in 21-day-old rat.

P–308 - Appearance of nicotine-sensitivity on adrenaline output from adrenals by starvation in 21-day-old rat.

Effect of cilnidipine, a novel dihydropyridine Ca2+ channel blocker, on adrenal catecholamine secretion in anesthetized dogs.

We investigated the effect of cilnidipine, a novel dihydropyridine Ca2+ channel blocker possessing blocking actions on N-type and L-type voltage-dependent Ca2+ channels (VDCCs), in comparison with the L-type VDCC blocker nifedipine, on adrenal catecholamine secretion in response to splanchnic nerve stimulation (SNS), acetylcholine (ACh), the nicotinic receptor stimulant 1,1-dimethyl-4-phenyl-piperazinium (DMPP), and muscarine in anesthetized dogs. Ca2+ channel blockers and cholinergic agonists were infused and injected, respectively, into the adrenal gland through the phrenicoabdominal artery. Cilnidipine (0.3-3 microg/min) inhibited increases in both epinephrine (EPI) and norepinephrine (NE) output induced by SNS (2 Hz), ACh (1.5 microg), and DMPP (0.2 microg). However, cilnidipine inhibited increase in NE output induced by muscarine (1 microg) without affecting increase in EPI output. Nifedipine (0.3-3 microg/min) inhibited the ACh- and DMPP-induced increases in EPI and NE output without affecting the SNS- and muscarine-induced increases in EPI and NE output. From these results, it seems likely that the inhibition by cilnidipine of the SNS-induced EPI and NE secretion and of the muscarine-induced NE secretion is related to its blocking action on N-type VDCCs.

The non-neurogenic catecholamine response of the fetal adrenal to hypoxia is dependent on activation of voltage sensitive Ca 2+ channels

We have investigated the cellular mechanisms underlying the catecholamine response of the fetal sheep adrenal to hypoxia before and after the development of adrenal innervation. Adrenals were collected before (80–100 days gestation: n = 7) and after (135–146 days gestation: n = 10) development of innervation and retrogradely perfused with oxygenated Krebs bicarbonate buffer in vitro via the renal vein. Adrenal hypoxia was induced by perfusion with hypoxic Krebs buffer ( pO 2 = 46.7 ± 2.4 mm Hg) for 30 min periods in the presence and absence of hexamethonium (500 μM), Ca 2+ (2.5 mM), nifedipine (1 μM) and KCl (10 mM). Hypoxia stimulated an increase ( P < 0.001) in the output of noradrenaline at 80–100 days (3 min pre hypoxia, 0.18 ± 0.07 nmol/3 min; 20 min hypoxia, 0.74 ± 0.22 nmol/3 min) and at 135–146 days (3 min pre hypoxia, 0.53 ± 0.20 nmol/3 min; 20 min hypoxia, 1.71 ± 0.85 nmol/3 min). Adrenaline output was also higher ( P < 0.001) than basal values (80–100 days, 0.11 ± 0.06 nmol/3 min; 135–146 days, 0.53 ± 0.15 nmol/3 min) after 20 min hypoxia (0.41 ± 0.20 nmol/3 min and 1.35 ± 0.56 nmol/3 min respectively). The catecholamine responses to hypoxia were abolished by removal of Ca 2+ from the adrenal perfusate. There was a reduction ( P < 0.05) in the catecholamine secretory response to hypoxia in the presence of nifedipine. Noradrenaline output decreased from 4.33 ± 0.84 nmol/30 min to 0.16 ± 0.49 nmol/30 min and adrenaline output decreased from 3.16 ± 1.66 nmol/30 min to −0.01 ± 0.24 nmol/30 min in the presence of nifedipine. The fetal adrenal secretes catecholamines by a direct or non-neurogenic mechanism in response to hypoxia. This secretory response is dependent on the activation of voltage sensitive Ca 2+ channels in the chromaffin cell membrane.