Norepinephrine Output Research Articles

Muscarinic and nicotinic mechanisms in the responses of the adrenal medulla of the dog and cat to reflex stimuli and to cholinomimetic drugs.

In isolated perfused adrenal glands of the cat, muscarinic and nicotinic agonists selectively released adrenaline and noradrenaline respectively. In isolated perfused adrenal glands of the dog, the output of adrenaline and noradrenaline remained in a fixed ratio at rest and when stimulated by muscarinic or by nicotinic agonists. In the anaesthetized dog, a combination of muscarinic and nicotinic antagonists was needed to block reflex responses of the adrenal medulla. A nicotinic antagonist was more effective in blocking the baroreceptor reflex response than the chemoreceptor reflex response.

Circadian variation of catecholamine excretion in rats: Correlation with locomotor activity and effects of drugs

Rats housed in metabolic cages were used to study the circadian variation in the urinary excretion of free catecholamines. Small samples of urine (25–100 μl) were analyzed for adrenaline, noradrenaline and dopamine by high pressure liquid chromatography (HPLC) and electrochemical detection. Various ways in which the values for excretion of catecholamines can be expressed (per min; per ml; per mmol creatinine; as ratio over dopamine) were calculated and discussed. Correction for excretion of creatinine resulted in the lowest variations coefficient among the experimental data. The correction for creatinine removed the circadian rhythm present in the output of noradrenaline (NA) and dopamine (DA). Adrenaline corrected for creatinine still displayed a pronounced circadian variation which was related to the overall locomotor activity of the animals (as recorded by photocells). Collection of 1 hr samples instead of 3 hr samples resulted in a worsening of the relationship between the excretion of adrenaline and locomotor activity. Finally, the possibility that the DA antagonist haloperidol, the DA agonist dipropyl-5,6-2-amino-6,7-dihydroxytetrahydronaphtalene (dipropyl-5,6 ADTN) and the α-antagonist phentolamine, could modify the excretion of free urinary catecholamines was investigated. Haloperidol and 5,6-dipropyl-ADTN did not change the output of the catecholamines, but phentolamine induced a strong increase in the excretion of NA. The latter observation suggest that at least part of the excretion of NA may originate from peripheral noradrenergic neurotransmission.

CCK and other peptides modulate hypothalamic norepinephrine release in the rat: Dependence on hunger or satiety

The purpose of this investigation was to determine the functional relationship between putative satiety peptides and endogenous norepinephrine (NE) activity in the hypothalamus. Permanent guide cannulae for push-pull perfusion were implanted stereotaxically in Sprague-Dawley rats so as to rest above the medial or lateral hypothalamus (LH). Post-operatively, the animals were either satiated with food and water, both available ad lib, or fasted for 18–22 hr prior to an experiment. To perfuse a site in the LH, paraventricular (PVN) or ventromedial nucleus (VMN), a concentric 23–29 ga push-pull cannula system was lowered to a pre-determined site, in most cases after catecholamine stores had been pre-labeled with [ 3H]-NE. During control tests, an artificial CSF was perfused at a rate of 20–25 μl/min for 5–8 min with a 5 min interval between each sample. The addition of cholecystokinin (CCK) in a concentration of 2.0–6.0 ng/μl to the CSF perfused in PVN or VMN of the satiated rat enhanced the efflux of NE; however, in the fasted animal CCK often suppressed the catecholamine's release. Perfused in the LH, CCK exerted opposite effects, typically augmenting NE output when the rat was fasted but not affecting the amine's activity during the sated condition. Proglumide (1.2 μg/μl) attenuated CCK's effect in releasing NE when the antagonist was perfused in the PVN of the satiated rat. Similar experiments in which neurotensin (NT) was perfused in the LH, PVN and VMN revealed virtually the same inverse effects on NE release in the fasted and satiated rat, which again were anatomically specific. Finally, insulin and 2-deoxy-D-glucose (2-DG) exerted similar state-dependent effects on the release of NE within LH and PVN. Overall, the results suggest that CCK or other neuroactive peptide could serve as a “neuromodulator” of the pre-synaptic release of NE within classical hypothalamic structures which are thought to underlie both hunger and satiety. The state-dependent nature of the peptides' activity on the noradrenergic feeding mechanism implies that these substances constitute a pivitol portion of the profile of factors which impinge functionally upon the hypothalamic neurons responsible for the feeding response and its cessation.

Urinary monoamines and monoamine metabolites in subtypes of unipolar depressive disorder and normal controls.

An examination was made of urinary catecholamine and metabolite outputs in 28 unipolar depressed patients and 25 normal controls. The total group of depressed patients had significantly higher urinary outputs of norepinephrine (NE) and its metabolite normetanephrine (NM), and significantly lower urinary outputs of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC), than controls. Patients who met DSM-III criteria for a major depressive episode with melancholia (N = 8) had significantly higher urinary outputs of normetanephrine than controls, whereas patients with a major depressive episode without melancholia (N = 7) and dysthymic disorder patients (N = 8) had levels comparable with controls. We postulate that the higher urinary outputs of norepinephrine and its metabolite, normetanephrine, reflect dysregulation of the sympathetic nervous system in depression.

Measurement of endogenous noradrenaline release in the rat cerebral cortex in vivo by transcortical dialysis: effects of drugs affecting noradrenergic transmission.

The release of endogenous noradrenaline was measured in the cerebral cortex of the halothane-anesthetized rat by using the technique of brain dialysis coupled to a radioenzymatic assay. A thin dialysis tube was inserted transversally in the cerebral cortex (transcortical dialysis) and perfused with Ringer medium (2 microliter min-1). Under basal conditions, the cortical output of noradrenaline was stable over a period of at least 6 h and amounted to 8.7 pg/20 min (not corrected for recovery). Histological control of the perfused area revealed very little damage and normal morphology in the vicinity of the dialysis tube. Omission of calcium from the perfusion medium caused a marked drop in cortical noradrenaline output. Bilateral electrical stimulation (for 10 min) of the ascending noradrenergic pathways in the medial forebrain bundle caused a frequency-dependent increase in cortical noradrenaline output over the range 5-20 Hz. Stimulation at a higher frequency (50 Hz) resulted in a levelling off of the increase in cortical noradrenaline release. Systemic administration of the dopamine-beta-hydroxylase inhibitor bis-(4-methyl-1-homopiperazinylthiocarbonyl) disulfide (FLA 63) (25 mg/kg i.p.) markedly reduced, whereas injection of the monoamine oxidase inhibitor pargyline (75 mg/kg i.p.) resulted in a progressive increase in, cortical noradrenaline output. d-Amphetamine (2 mg/kg i.p.) provoked a sharp increase in cortical noradrenaline release (+450% over basal values within 40 min). Desmethylimipramine (10 mg/kg i.p.) produced a twofold increase of cortical noradrenaline release. Finally, idazoxan (20 mg/kg i.p.) and clonidine (0.3 mg/kg i.p.), respectively, increased and decreased the release of noradrenaline from the cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Increases in blood flow from the adrenal gland following medial hypothalamic stimulation in the cat

Medial hypothalamic sites previously shown to elicit either flight or defense were stimulated in the anesthetized cat. The rate of blood flow from the adrenolumbar (AL) vein ipsilateral to the side of stimulation was measured, as well as the adrenal output of norepinephrine and epinephrine (E). Stimulation at nearly 15% of the hypothalamic sites increased ipsilateral AL venous flow more than 20% over baseline rates. These sites also significantly increased heart rate, mean arterial pressure, and output of E from the ipsilateral adrenal gland. These observations suggest that hypothalamic sites where stimulation increased AL venous flow may overlap with regions that selectively mediate the release of E from the adrenal medulla.

Co-release of neuropeptide Y and catecholamines upon adrenal activation in the cat.

The release of neuropeptide Y (NPY)-like immunoreactivity (-LI) in relation to catecholamines from the cat adrenal was studied in anaesthetized animals. Abdominal surgery increased plasma levels of NPY-LI from 65 +/- 6 to 149 +/- 26 pmol l-1. A positive veno-arterial concentration gradient over the adrenal gland was found for both NPY-LI, adrenaline (Adr) and noradrenaline (NA) during basal conditions. Asphyxia for 2 min increased the output of both NPY-LI and catecholamines from the adrenal. Electrical stimulation of the splanchnic nerve caused a marked increase in adrenal output of NPY-LI and catecholamines. The adrenal content of NPY-LI, as well as the release of NPY-LI from the adrenal, was at least 1000-fold lower on a molar basis than that of catecholamines. The concentration of NPY-LI in the adrenal vein upon splanchnic nerve stimulation was in the nM range. Reversed-phase HPLC characterization revealed that NPY-LI in the adrenal, and in the adrenal venous plasma collected during splanchnic nerve stimulation, was closely related to synthetic porcine NPY. Stimulation with bursts of 20 Hz for 1 S with 10 s intervals for 2 min caused a four-fold higher output of NPY-LI and Adr compared to a continuous stimulation with 2 Hz, giving the same number of impulses. The NA output, however, was only slightly increased by burst stimulation. Guanethidine did not reduce the adrenal output of NPY-LI or catecholamines induced by splanchnic nerve stimulation, while the release was abolished by chlorisondamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma catecholamines associated with hypothalamically-elicited flight behavior

Hypothalamic sites were selected which elicited flight (escape) behavior in the freely moving cat. Sympatho-adrenal (SA) activation was determined by measuring the levels of norepinephrine (NE) and epinephrine (E) in bilateral adrenolumbar and peripheral venous plasma following stimulation of these 29 hypothalamic sites in 18 anesthetized cats. Heart rate (HR) and mean arterial pressure (MAP) were continuously monitored to permit comparisons between SA and cardiovascular (CV) activation. The most frequent SA response was a bilateral increase in the output of NE and E from the adrenal medulla ⩾ 10 ng/min. Increases in MAP during hypothalamic stimulation were significantly correlated with bilateral increases in both adrenal CAs, while increases in HR were significantly correlated with increases in peripheral venous NE. The data suggest that hypothalamic regions which elicit flight behavior overlap with regions that activate the adrenal medullary and CV systems. The SA activation that accompanied hypothalamically-elicited escape is compared to SA activation associated with hypothalamically-elicited affective defense.

Bereavement and catecholamines

Urinary catecholamine output was studied in 59 middle-aged and elderly persons who were either acutely bereaved ( n=39) or threatened with the loss of a spouse ( n=20). The study was done with the hypothesis that urinary catecholamine output would be elevated among the bereaved subjects both in comparison to norms in the literature for non-stressed controls and to the group of subjects who were threatened with a loss. It was also expected that individually high measures of psychological distress would be associated with high urinary catecholamines. Twenty-four hour urinary output of norepinephrine and epinephrine was observed to be higher than normal during acute bereavement but was not associated with depression scores. No differences were found between those who had experienced an actual loss two months earlier and those who were threatened with a loss. Expected relationships between indices of psychological distress and catecholamine output were not observed. Finally, an association was found between increasing age and higher levels of urinary norepinephrine and epinephrine output among acutely bereaved subjects, suggesting that the adaptation of the sympathetic-adrenal medullary system to stress among older persons is slower.

Catecholamine excretion and beta-adrenergic responsiveness in estrogen-treated rats.

Chronic treatment with an estrogenic agent is known to reduce the responsiveness to beta-adrenergic stimulation in rats. To assess the possibility that endogenously produced catecholamines may play a role in this phenomenon, female rats were treated either with implanted Silastic tubes containing estradiol benzoate (26 micrograms/kg/day) or with empty tubes. After 12 weeks of treatment, the dipsogenic, colonic temperature and tail skin temperature responses to acute administration of the beta-adrenoceptor agonist, isoproterenol, were blunted compared to controls. Each of these responses was negatively correlated with serum estradiol concentration measured by radioimmunoassay. Urinary norepinephrine output was elevated significantly in treated rats during a 24-hour basal period. During a 2-hour exposure to air at 4 degrees C, urinary outputs of norepinephrine, epinephrine, and dopamine were elevated significantly above those of controls. There were significant positive correlations between plasma estradiol concentration and the outputs of each of the above catecholamines during the 24-hour basal period and during cold exposure, with norepinephrine being the most strongly correlated. Dipsogenic and metabolic (tail skin and colonic temperature) responses to administration of isoproterenol were negatively correlated with catecholamine excretion during both the basal 24-hour period and during cold exposure. These results suggest that reduced beta-adrenergic responsiveness in estrogen-treated rats may have resulted from down-regulation of beta-adrenoceptors associated with increased secretion of catecholamines induced by chronic estrogen treatment.

イヌ鼻粘膜血管とアセチルコリン受容体

It has been established that acetylcholine causes peripheral vasodilatation. Recent studies with in vitro muscle tension detecting devices suggest that, at least in large blood vessels, higher concentrations of the Cholinergic transmitters cause vasoconstriction. Vasodilating responses to acetylcholine are indirect and can be evoked either by decreasing the norepinephrine output from the adrenergic nerve terminal, or by stimulating the endothelial cells to generate yet unknown relaxing agents. In our experiments with in vitro preparations of the vascular smooth muscle of the canine nasal mucosa, the three above-mentioned cholinergic receptors (adrenergic nerve endings, vascular smooth muscle cells, and endothelial structures) were demonstrated. The cholinergic contractions were Ca2+ dependent.

Inhibition by Prostaglandins of Adrenergic Transmission in the Left Ventricular Myocardium of Anesthetized Dogs

In the intact left ventricle of pentobarbital-anesthetized dogs, we have investigated the influence of prostaglandins on cardiac adrenergic neuroeffector events. The positive inotropic response (dP/dtmax) and the coronary sinus output of norepinephrine (NE) elicited by left cardiac sympathetic nerve stimulation as well as the contractile response produced by intracoronary injections of NE were studied before and after prostaglandin synthesis inhibition, and also before and during intracoronary infusion of PGE2 and PGI2. Cardiac sympathetic nerve stimulation (1-4 Hz) and intracoronary injections of NE (30-120 ng/kg) produced frequency- and dose-related positive inotropic effects, respectively. Administration of indomethacin (10 mg/kg i.v.) augmented the increase in left ventricular dP/dtmax elicited by left cardiac sympathetic nerve stimulation or intracoronary NE injection. In indomethacin pretreated dogs, intracoronary PGE2 (30 ng kg-1 min-1) or PGI2 (60 ng kg-1 min-1) attenuated the positive inotropic effect produced by left cardiac sympathetic nerve stimulation or intracoronary injections of NE. The increase in coronary sinus output of NE elicited by cardiac sympathetic nerve stimulation was enhanced by indomethacin and attenuated during intracoronary infusion of PGE2 and PGI2. These data suggest that prostaglandins synthesized in the heart inhibit cardiac adrenergic transmission in the left ventricle in vivo by reducing release of NE elicited by left cardiac sympathetic nerve stimulation and also by attenuating the action of the neurotransmitter at effector cells.

Substance P given intrathecally at the spinal T9 level increases adrenal output of adrenaline and noradrenaline in the rat

Administration of 10 μg of substance P intrathecally to the spinal T 9 level of the adult rat. anaesthetized with urethane, provoked an increase in free catecholamines in plasma taken from the inferior vena cava. Adrenaline levels at l min after administration were154.8 ± 10.8% (mean±SE;n = 11) of preadministration levels and noradrenaline levels were153.5 ± 11.8% of preadministration levels. Differences between the values of free catecholamines in animals given substance P vs those given vehicle only were statistically significant at 1 and 10 min postinjection, but not at 30 min. Administration of a substance P analogue with central antagonistic properties 15 min before substance P was given prevented expression of the effects of substance P. These results suggest that substance P may be an excitatory chemical mediator of synaptic transmission in spinal pathways controlling adrenal medullary output. Thus dysfunction of substance P mechanisms may underlie some animal models of hypertension and may be involved in some cases of essential hypertension in man as well as in autonomie dysfunction associated with some neurological entities.

Behavioural and endocrine reactions in boys scoring high on Sennton neurotic scale viewing an exciting and partly violent movie and the importance of social support

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.

Adaptation to exercise in the cold.

The winter athlete has several potential tactics for sustaining body temperature in the face of severe cold. An increase in the intensity of physical activity may be counter-productive because of increased respiratory heat loss, increased air or water movement over the body surface, and a pumping of air or water beneath the clothing. Shivering can generate heat at a rate of 10 to 15 kJ/min, but it impairs skilled performance, while the resultant glycogen usage hastens the onset of fatigue and mental confusion. Non-shivering thermogenesis could arise in either brown adipose tissue or white fat. Brown adipose tissue generates heat by the action of free fatty acids in uncoupling mitochondrial electron transport, and by noradrenaline-induced membrane depolarisation and sodium pumping. The existence of brown adipose tissue in human adults is controversial, and although there are theoretical mechanisms of heat production in white fat, their contribution to the maintenance of body temperature is small. Acclimatisation to cold develops over the course of about 10 days, and in humans the primary change is an insulative, hypothermic type of response; this reflects the intermittent nature of most occupational and athletic exposures to cold. Nevertheless, with more sustained exposure to cold air or water, humans can apparently develop the humoral type of acclimatisation described in small mammals, with an increased output of noradrenaline and/or thyroxine. The associated mobilisation of free fatty acids suggests the possibility of using winter sport as a pleasant method of treating obesity. In men, a combination of moderate exercise and facial cooling induces a substantial fat loss over a 1- to 2-week period, with an associated ketonuria, proteinuria, and increase of body mass. Possible factors contributing to this fat loss include: (a) a small energy deficit; (b) the energy cost of synthesising new lean tissue; (c) energy loss through the storage and excretion of ketone bodies; (d) catecholamine-induced 'futile' metabolic cycles with increased resting metabolism; and (e) a specific reaction to cold dehydration. Current limitations for the clinical application of such treatment include uncertainty regarding optimal environmental conditions, concern over possible pathological reactions to cold, and suggestions of a less satisfactory fat mobilisation in female patients. Possible interactions between physical fitness and metabolic reactions to cold remain controversial.(ABSTRACT TRUNCATED AT 400 WORDS)

Local Modulation of Adrenergic Neurotransmission in Blood Vessels

Norepinephrine, released from sympathetic nerve terminals, has a key role in adjusting continuously the performance of the cardiovascular system. Although the amount of transmitter released depends primarily on the degree of activation of postganglionic sympathetic fibers, local metabolites and circulating vasoactive substances, in addition to affecting smooth-muscle cells directly, alter the amount of norepinephrine released. Thus, metabolic acidosis, an increase in potassium ions and in osmolality reduce the output of norepinephrine in the face of a constant frequency of stimulation of the postganglionic fibers. Many receptors have been identified on the prejunctional nerves which, when activated, can increase or decrease transmitter release. Those agonists which decrease it include adenosine and the adenine nucleotides, and norepinephrine, acetylcholine, histamine, and serotonin, acting on purinergic, alpha 2-adrenoceptors, muscarinic, H2-histaminergic and S1-serotoninergic receptors, respectively. Those that increase transmitter release include epinephrine (acting on beta 2-adrenoceptors) and angiotensin II. Part of the action of certain drugs is due to their prejunctional effects. Thus, cardiac glycosides cause a release of norepinephrine, and the antidepressant drug amitriptyline causes inhibition of prejunctional alpha-adrenoceptors and muscarinic receptors. Local changes in temperature also have complex actions on the neuroeffector junction and the vascular smooth muscle, which are of prime importance for cutaneous vessels.

High urinary norepinephrine excretion in major depressive disorders: effects of a new type of MAO inhibitor (Moclobemide, RO 11-1163).

The urinary excretion rates of norepinephrine were assayed in 26 patients diagnosed as major depressive disorders (primary, unipolar), before and after 14 days of treatment with the monoamine oxidase inhibitor Moclobemide (Ro 11-1163). A standardized 1-h urine collection procedure was used and norepinephrine was assayed by liquid chromatography with electrochemical detection. Norepinephrine was found significantly increased in depressed patients when compared with a control population. The psychotic patients showed the highest excretion rates although they were not significantly different from the endogenous (non-psychotic) group. Urinary norepinephrine output significantly decreased after 14 days of treatment with Moclobemide. This decrease was also marked in those patients that did not show any therapeutic effect. A clear antidepressant effect, shown by a significant decrease of the Hamilton Scale scores for depression, was apparent as early as the 7th day. Increased norepinephrine in melancholic patients was taken as a presumptive indication of altered sympathetic activity.

Effect of beta-adrenergic blockade on in vivo norepinephrine release in canine heart.

The beta-adrenergic blockade-induced reduction in myocardial norepinephrine overflow during sympathetic stimulation was examined by use of the multiple indicator-dilution technique. A kinetic model incorporating the effects of flow, capillary permeability surface product for norepinephrine, the interstitial uptake rate constant for neurotransmitter, and plasma norepinephrine input and output values was used to estimate the rate of local release of norepinephrine into the interstitial space. The model was tested by first examining the effects of two drugs that increase myocardial norepinephrine overflow during sympathetic stimulation by differing mechanisms: desmethylimipramine, a norepinephrine uptake inhibitor, and phentolamine, an alpha-adrenergic blocker. The uptake inhibitor was demonstrated to reduce interstitial uptake and the alpha-blocker to increase local neurotransmitter release, without change in blood flow. The beta-adrenergic blocker, in contrast, reduced coronary blood flow and decreased the capillary norepinephrine permeability surface product but did not change the rate of local release. The decreased norepinephrine overflow after beta-blockade was deduced to result from the decrease in transcapillary flux and secondary increase in interstitial uptake.

Attenuation by captopril of pressor responses to sympathetic stimuli: effects of procedures reducing activity of the renin-angiotensin system.

Low doses (0.1-1.0 mg/kg) of the converting enzyme inhibitor captopril given intravenously to pithed rats were followed by long lasting falls in systolic and diastolic arterial blood pressures. Concomitantly pressor responses were reduced to either electrical stimulation of the thoraco-lumbar sympathetic outflow or intravenous injection of the ganglion stimulant McNeil-A-343. Positive chronotropic responses of the heart to cardiac nerve stimulation were unchanged after relatively large doses of the drug (3.0 mg/kg). The reductions in arterial blood pressure and pressor responses to McNeil-A-343 caused by captopril persisted following beta-adrenoreceptor blockade, renal sympathectomy or unilateral nephrectomy, but did not occur after acute bilateral nephrectomy nor during sodium and water retention due to unilateral nephrectomy plus subacute administration of desoxycorticosterone and saline. Pressor responses to noradrenaline were reduced after 1.0 mg/kg captopril i.v. whereas those to methoxamine or vasopressin were unaltered after 5.0 mg/kg. It is concluded that in the rat, after elimination of sympathetic tone by pithing, the level of the arterial blood pressure and the magnitude of pressor responses to peripheral sympathetic nerve activation depend on the basal activity of the renin-angiotensin system. This maintains sufficient angiotensin II production to ensure retention of some tone in resistance vessels together with presynaptic augmentation of noradrenaline output at a sympathetic postganglionic nerve endings. The latter effects are abolished after converting enzyme inhibition with captopril, consequent to reduced tissue levels of angiotensin II and perhaps potentiation of the actions of bradykinin.

Reliability of urinary monoamine and metabolite output measurements in depressed patients.

The authors measured urinary monoamines and their metabolite outputs in 12 unmedicated depressed patients. Output of 3-methoxy-4-hydroxy-phenylglycol and vanillylmandelic acid proved to be relatively stable from one sample to another. An average of at least two measures provided data with a meaningful reliability for normetanephrine, serotonin, and homovanillic acid output. Output of dopamine, norepinephrine, 5-hydroxyindoleacetic acid, and phenylethylamine was highly variable over time.