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The object was to investigate the effect of various perinatal conditions particularly cooling and asphyxia on the noradrenaline (NA) turnover in the foetal rat brain. The ratios between the noradrenergic metabolite 3-methoxy-4-hydroxy phenyl-ethylene glycol-sulphate (MHPG) and noradrenaline were determined as indexes of NA-turnover in the cortex and the pons-medulla of the foetal rat brain using high pressure liquid chromatography (HPLC). Rat foetuses were externalized by caesarean section performed on a spinally anaesthesized highly pregnant rat mother. One uterine horn was used as control while the other was exposed to externalization, simulated uterine contractions, cooling or asphyxia. Externalization per se and simulated uterine contractions did not cause any significant change in the NA-turnover. Cooling at 25 degrees C for 20 min caused a significant increase in NA-turnover in the cortex while a significant decrease was observed after 10 min of asphyxia in both the cortex and the pons-medulla and after 15 min in the cortex. We conclude that externalization and simulated uterine contractions per se do not seem to affect the augmented NA-turnover at birth. Cooling caused an increase suggesting a potentiating role on NA-turnover in conjunction with the externalization. On the other hand NA-turnover was depressed by asphyxia, suggesting that the level of oxygen is important for NA neuron activity.

Effects of chronic high-altitude hypoxia on the remodeling of right ventricle were examined in three age groups of rats: 2, 6, and 18 mo. The extent of right ventricular (RV) hypertrophy (RVH) showed an age-associated diminution. RV cell size and pericellular fibrosis showed a significant increase in the 2- and 6-mo-old exposed rats but not in the 18-mo-old exposed rats compared with control. A hyperplasic response was underscored in the three exposed age groups but appeared less pronounced in the 18-mo-old rats. A significant decrease in the transient outward potassium current ( Ito) density was observed in RV cell only in the 2-mo-old exposed group compared with the control group. In the control group, there was a clear tendency for Ito density to decrease as a function of age. The sustained outward current density was modified neither by the hypoxia condition nor by the age. Neither the cytochrome c oxidase activity nor the heat shock protein 72 content in the RV was altered after hypoxic exposure regardless of age. The norepinephrine content in the RV was significantly decreased in each age group exposed to hypoxia when compared with their age-matched control group. Our findings indicate that the remodeling (at morphological and electrophysiological levels) induced by chronic hypoxia in the RV can be decreased by the natural aging process.

The aim of the present study was to analyse electric resistivity at different ambient temperatures between 300 to 20K in the frog sciatic nerve and salmon sperm DNA. When the electrical contacts were leaned just into the sciatic nerve, an increase of the sciatic nerve resistivity was observed for 240 KT300 K and a rise of electrical conductivity was apparent below 240 K. This dependence is generally associated with a semiconductor behaviour. Once the sciatic nerve temperature was driven below 250K, the resistivity abruptly decreased and then at temperatures lower than 234 K, it remained constant and close to one tenth of its ambient temperature value. By contrast, when the electrical contacts were leaned into Salmon sperm DNA, the resistivity remained constant between 300K to 20K, showing a high electrical stability at low temperature. Thus, we report the existence of a new form of electric conductivity in the sciatic nerve at low ambient temperature, which in turn has many electric similarities with inorganic or organic superconductors, whereas temperature failed to alter DNA electrical properties until 20K.

The object was to investigate the effect of various perinatal conditions particularly cooling and asphyxia on the noradrenaline (NA) turnover in the foetal rat brain. The ratios between the noradrenergic metabolite 3-methoxy-4-hydroxy phenyl-ethylene glycol-sulphate (MHPG) and noradrenaline were determined as indexes of NA-turnover in the cortex and the pons-medulla of the foetal rat brain using high pressure liquid chromatography (HPLC). Rat foetuses were externalized by caesarean section performed on a spinally anaesthesized highly pregnant rat mother. One uterine horn was used as control while the other was exposed to externalization, simulated uterine contractions, cooling or asphyxia. Externalization per se and simulated uterine contractions did not cause any significant change in the NA-turnover. Cooling at 25 degrees C for 20 min caused a significant increase in NA-turnover in the cortex while a significant decrease was observed after 10 min of asphyxia in both the cortex and the pons-medulla and after 15 min in the cortex. We conclude that externalization and simulated uterine contractions per se do not seem to affect the augmented NA-turnover at birth. Cooling caused an increase suggesting a potentiating role on NA-turnover in conjunction with the externalization. On the other hand NA-turnover was depressed by asphyxia, suggesting that the level of oxygen is important for NA neuron activity.

We compared in albino and pigmented rats the early effect of unilateral labyrinthectomy (UL) on the concentrations of monoamines (norepinephrine, dopamine, serotonin) and their respective metabolites--3-methoxy,4-hydroxyphenylglycol (MHPG), 3,4-dihydroxy-phenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5HIAA)--in medial vestibular nuclei (MVN), locus coeruleus, raphe dorsalis, and cochlear nuclei. The study was conducted 6 hours after UL in both strains, differing by the functional optokinetic responses of their central vestibular neurons and the time-course of their vestibular compensation. The results show that the monoaminergic changes are different in the two rat strains. In the MVN of albino rats, there was a bilateral increase of MHPG and an ipsilateral increase of dopamine suggesting activation of norepinephrine synthesis and metabolism, whereas no such changes were observed in the MVN of pigmented rats. On the other hand, the simultaneous increase of norepinephrine and DOPAC observed in the contralateral locus coeruleus of albino rats suggested enhanced norepinephrine synthesis, whereas in pigmented rats the decreased norepinephrine content found in the ipsilateral locus coeruleus might reflect an earlier strong stimulation of NE release. These biochemical results confirm the relevant role of locus coeruleus noradrenergic innervation in vestibular compensation and also point out the involvement of norepinephrine of the MVN in the early stages of this process. The different strain-related noradrenergic responses observed on the 6th hour suggest that the involvement of central norepinephrine, particularly from locus coeruleus innervation, may be more crucial and more sustained in the albino than in pigmented rats. No serotonin and 5HIAA changes were found in either brainstem nuclei of albino rats. In contrast, the increase of the ratio 5HIAA/5HT observed in raphe dorsalis, in ipsilateral locus coeruleus, and in both sides of MVN of pigmented rats suggested that UL induced an extended and enhanced utilization of 5HT in this strain.

The norepinephrine (NE) content in discrete brain areas and the vasopressin content in the neurohypophysial system were assessed in rats after a 9-d spaceflight and after a recovery period (9 d). The NE content in the locus coeruleus decreased significantly in spaceflight rats (2.9 +/- 0.3 vs. 8.9 +/- 0.7 pmol.structure-1 for control rats, p0.001), but showed no difference between control and flight animals after a 9-d recovery. These findings were probably due to an acute stress undergone during landing. The NE content was unchanged in the A2 and A5 cell groups. In rats flown aboard SLS-1, the vasopressin content was increased in the posterior pituitary (1.47 +/- 0.1 vs. 0.86 +/- 0.1 micrograms.structure-1, for control rats, p0.01), and was significantly decreased in the hypothalamus (8.95 +/- 2.0 vs. 17.6 +/- 2.2 ng.structure-1, for control rats, p0.05). We conclude that the NE depletion in the locus coeruleus and the alteration in vasopressin release were consistent with an acute stress, likely occurring during and/or after landing. These changes tend to mask the actual neuroendocrine modifications caused by microgravity.

After a 9-d hindlimb suspension, the turnover rate of norepinephrine (NE) in rats was determined in A1, A2 (rostral and caudal), A5 and A6 cell groups, as well as in peripheral target organs (heart and kidneys). The NE turnover rate decreased after hindlimb suspension respectively in caudal A2 (67.5%, p0.001), rostral A2 (63%, p0.001) and in A5 cell groups (62.5%, p0.001), but remained unchanged in A1 and A6 regions. The peripheral sympathetic outflow response was selectively modified: in suspended rats, the NE turnover was mainly decreased in atria (79%, p0.001) and in ventricles (44%, p0.001); there were no biochemical changes in kidneys. It was concluded that a 9-d hindlimb suspension: 1) impaired the noradrenergic neuron activity of A2 and A5 cell groups, which are involved in the central cardiovascular regulation, and particularly in the baroreceptor reflex mechanism; and 2) mainly altered the cardiac NE turnover and induced a selective response of peripheral target organs.

Although hypoxia and hypercapnia are both able to excite the carotid body chemoreceptor activity, several lines of evidence suggest that these two stimuli may operate through different mechanisms (Acker, 1980; Bisgard et al., 1986; Donnelly et al., 1981; Fitzgerald et al., 1983; Mulligan and Lahiri, 1982). In acute hypoxia, dopamine (DA) is released from glomus cells and acts as a neuromodulator of the chemosensory excitation (Hanbauer and Hellstrom, 1978; Llados and Zapata, 1978). The two catecholamines, DA and norepinephrine (NE), stored in the carotid body are also involved in the chemoreceptor response to long-term hypoxia (Hanbauer et al., 1981; Pequignot et al., 1987). In contrast, there was no release of DA in response to acute hypercapnia (Fitzgerald et al., 1983) and the content of catecholamines in the carotid body remained unchanged after long-term exposure to hypercapnia (Hellstrom et al., 1989). Because hypercapnia, unlike hypoxia, may be largely sensed by central chemoreceptors, it is conceivable that the carotid chemoreceptor response to hypercapnia may be considerably altered by a potent efferent regulatory influence.

In recent years, several studies have been performed to examine the influence of systemic hypertension on function and morphology of the carotid bodies. It has been shown that both function and morphology of these peripheral arterial chemoreceptors are altered. Most morphological investigations were carried out in rats. Up to now, the carotid bodies (CB) of 3 strains with spontaneous hypertension (OKAMOTO-AOKI (SHR), New Zealand (GH), Milan (MH), and those with renal (secondary) hypertension have been examined (Alho et al., 1984; Barer et al., 1987; Habeck et al., 1985, 1987a; Pallot and Barer, 1985; Smith et al., 1984). Depending on the strain used different morphological and biochemical findings were obtained.

Still, conclusive evidence is lacking whether or not the carotid body type-I cells are a structurally and functionally homogenous group of cells or constitute more than one population of cells. Similarly, little is known about altered characteristics of the carotid body elements in hypoxia. To address these questions we have applied lectin histochemistry as a tool in our attempts to differentiate between the tissue elements in the carotid body.

Exposure to prolonged hypoxia causes a gradual increase in pulmonary ventilation above the acute hypoxic response despite a decrease in the blood gas stimulus levels resulting from hyperventilation (1). This phenomenon referred to as ventilatory acclimatization to hypoxia has been observed in all mammalian species studied to date. Evidence has accumulated indicating that the carotid body chemoreceptors are essential to the process of ventilatory acclimatization to long-term hypoxia (2–5). The importance of the carotid bodies in this physiological adaptation is stressed further by a number of morphological, biochemical, and functional alterations of the organ in response to long-term hypoxic exposure.

The vagal branches, the recurrent and superior laryngeal nerves (RLN and SLN), which innervate the intrinsic muscles and the mucosa of the larynx, contain paraganglia in both humans and rat (1–3). These paraganglia resemble morphologically the carotid body and are composed of clusters of dense-cored vesicle cells, sustentacular cells, and thin-walled blood vessels. Unmyelinated nerve fibers occur in the connective tissue of the paraganglia, and nerve endings are in contact with the vesicle-containing cells (3). Histofluorescence studies have revealed the storage of catecholamines in the paraganglia of the rat, and biochemical analysis have shown that dopamine and noradrenaline are present in the laryngeal nerves, the amines probably being stored in the paraganglia (4). Another possible storage site of catecholamines in the laryngeal nerves is sympathetic nerve fibers located within the nerve trunks.

Objectifs Evaluation de l’effet de l’exposition aigue et subaigue a l’ozone en IRM. Materiels et methodes Dix-huit rats âges de 5 mois sont utilises. Les animaux sont maintenus dans une enceinte en plexiglas balayee par un flux d’air continu filtre. L’ozone est produit a partir d’une lampe UV placee sur le circuit d’air a l’entree de l’enceinte. Quatre groupes d’animaux sont soumis a une exposition d’ozone de 0,5 ppm en continue ou intermittente (12 h par jour) pendant 2 ou 6 jours. Trois rats controles sont soumis a flux d’air exclusif. Juste apres l’exposition (moins de 3 heures) les animaux sont images sur une IRM 2T apres inhalation de 6 ml d’Helium 3 a un debit de 2ml/s. Resultats Tous les animaux exposes a 6 jours d’ozone presentaient de larges troubles de ventilation predominant au niveau des apex pulmonaires. Les animaux exposes a 2 jours d’ozone et les controles ne presentaient pas de trouble de ventilation. Conclusion Le rat represente un bon modele pour l’etude des effets physiopathologiques de l’ozone car sa sensibilite a l’ozone est voisine de celle observee chez l’homme. La dose de 0,5 ppm chez le rat est equivalente a une dose de 0,1 ppm chez l’homme. Cette dose de 0,1 ppm est souvent depassee dans les pays industrialises en ete.

A number of arguments support the hypothesis that changes in urinary levels of MHPG sulfate and MHPG glucuronide respectively reflect central and peripheral norepinephrine metabolism (NE) in man. In this line, the daily excretion of both conjugates was determined in 36 depressed women comparatively to 23 healthy women in order to assess the extent and the central or peripheral location of their possible NE dysfunction. About 80% of the patients suffering from depression (6 endogenous, 19 neurotic, 11 reactive depressions) exhibited a central NE defect, as evidenced by low MHPG sulfate, and many of them had probably also diminished sympathetic activity, as suggested by low MHPG glucuronide. Clinical symptoms possibly related to the psychic state (mood alteration) or associated to sympathetic changes (anxiety, motor activity) respectively altered sulfate or glucuronide excretion. Sulfate (S) and glucuronide (G) MHPG excretions were significantly correlated in healthy subjects (r = 0.53, p = 0.01), thus supporting the concept of the functional link between central NE activity and sympathetic function. Such a correlation was not found in depressive patients. However the lack of significant changes in the mean ratio S/G in the patient subgroups suggests that as in normal subjects, central and peripheral NE activity As a conclusion, our work shows that urinary MHPG provides in depressed patients an index of the psychobiological state, involving central and peripheral components. Any factor acting on either of both components is able to modify MHGP excretion. The separate assay of sulfate and glucuronide MHPG allows-with some limitations-to define the relative changes of central and peripheral activity. As a whole, our data indicate that in the examined population, 80% had probably a central NE hypoactivity, also associated in a large number to a sympathetic dysfunction. These observations may have valuable physiopathologic and/or therapeutic implications.

Catecholamine content in the recurrent and superior laryngeal nerves (RLN and SLN) of the rat was analysed by high-performance liquid chromatography after surgical and chemical sympathectomy. Sympathectomy induced by repeated injections of guanethidine did not lead to any change in the dopamine (DA) level, whereas the noradrenaline (NA) content decreased by 68% and 64% respectively in the RLN and SLN. Surgical excision of the superior cervical ganglion (SCG) did not alter the level of DA in the SLN, but caused a 60% decrease of DA in the RLN. Removal of SCG did not affect the NA levels either in the RLN or in the SLN, unless it was combined with extirpation of the middle cervical ganglion, which induced a decrease in NA in both nerves. The results indicate that much of the DA in the laryngeal nerves is stored outside the sympathetic nerve fibres, probably in the small organs earlier characterized as endoneurial paraganglia.

Adrenergic response to exercise and the relationships between plasma catecholamines and blood energetic substrates were studied in sedentary men after 15 h of fasting. Subjects pedaled a bicycle ergometer until exhaustion at a work load approximating 80% maximal oxygen consumption. Working ability was diminished by the fast (P less than 0.025). Resting plasma norepinephrine level was increased by fasting. During exercise plasma epinephrine (E) and norepinephrine (NE) concentrations were more elevated in fasting subjects than in fed subjects. Plasma catecholamine (CA) levels in fasting men correlated with blood glucose, blood lactate, and plasma glycerol concentrations. There was no significative correlation between CA and plasma free fatty acid (FFA) levels. The increased adrenergic activity in fasting subjects correlated with reduced endurance time. This study emphasizes the role of CA release, probably combined with other hormonal factors, in the mobilization of energy substrates during submaximal exercise.

The catecholamine content in cochlear and facial nerves was determined using high-performance liquid chromatography coupled with electro-chemical detection. Minute amounts of norepinephrine were detected in both nerves in normal CBA/CBA mice and homozygotic jerker mouse mutants, whereas norepinephrine was found only in the facial nerve in the dancer heterozygotic mouse mutant. Dopamine and epinephrine were not detected in any of the mouse strains.

The aim of this study was to determine the effects of a 5-h weightlessness simulation (using supine bed rest or head-down tilt at -10 degrees = HDT) on plasma renin activity (PRA), aldosterone (PA), and catecholamines (epinephrine-E, norepinephrine-NE, and dopamine-DA) and to compare the results with those obtained with horizontal bed rest (BR), which is often taken as a control situation for simulation studies. Ten healthy young volunteers submitted to the three following postural tests: 7 h sitting; 1 h sitting, 5 h supine, and 1 h sitting; 1 h sitting, 5 h HDT, and 1 h sitting. Our results show that a 5-h HDT or BR induced a significant progressive increase in plasma volume (14.5% for HDT and 7% for BR) and a decrease in diastolic blood pressure (18% for HDT and 17% for BR), PRA (60% for HDT and 40% for BR), PA (63% for HDT and 60% for BR), and NE (20% for HDT and 25% for BR) compared to the sitting position. E decreased only in HDT, and DA was unchanged. We concluded that the main part of the cephalad shift is achieved by bed rest as reflected by changes in hematocrit and plasma protein concentration. The decrease in diastolic blood pressure, the inhibition of the renin-angiotensin aldosterone system (in part explained by a decrease in NE) are similar in BR and HDT. We demonstrate that the use of a relevant body position as control is a major concern when investigating the hormonal effects of HDT. If recumbency is chosen as the control situation in HDT studies, it is not surprising to observe only few changes when HDT is applied.

Rats were exposed to hypoxia (10% O2) for 1 and 3 weeks with or without daily injections of DL-propranolol (0.66 mg/kg i.p.). The structure of the carotid bodies was analyzed by light microscopical morphometry. Hypoxia induced enlargement of the carotid body due to enhanced vascularity and hypertrophy of glomic and interstitial tissues. The contents of dopamine and norepinephrine multiplied. Propranolol abolished the vasodilatory effect of hypoxia within the first week but did not prevent the other structural changes and the rise in catecholamine content. The data suggest that 1) the vaso-dilation elicited by long-term hypoxia may be controlled by beta-adrenoceptors; 2) the structural and biochemical events occurring in rat carotid body during long-term hypoxia seem to be controlled by different mechanisms.

The effects of normobaric hypoxia (10% O2) for 2, 7, 14 and 28 days on the dopamine (DA), norepinephrine (NE) and epinephrine (E) dynamics (content and utilization) were investigated in carotid bodies, adrenals, heart, kidneys and three sympathetic ganglia. The results indicate that long-term hypoxia elicited a complex and sustained stimulation of the sympathoadrenal system. Four striking features were evidenced: 1) In carotid bodies, the DA, and with a delay, the NE dynamics were greatly enhanced; 2) in sympathetic ganglia, DA was the only catecholamine whose metabolism was enhanced, suggesting a chemosensitive DA pool in ganglia; 3) in nerve terminals (heart and kidneys), at variance with ganglia, the stimulation under hypoxia was evidenced by the increase in NE metabolic rate; 4) no adaptation of the sympathoadrenal activity occurred after 28 days of hypoxia, except, perhaps, for adrenals.

The aim of our study was to investigate the endogenous origin of the three forms of 3-methoxy-4-hydroxyphenylglycol (MHPG) present in human urine and to further examine the hypothesis of an independent (peripheral or central) origin of glucuronide and sulfate conjugates. The urinary levels of free, sulfate, and glucuronide MHPG were determined in control subjects under normal conditions in relation to age, sex, and diet and in two experimental situations known to alter sympathetic activity. The mean daily excretion of total MHPG in a group of 14 men and 14 women was 1780 +/- 122 micrograms, with the free, sulfate, and the glucuronide representing 8% +/- 0.5%, 40% +/- 1.5%, and 52% +/- 1.6%, respectively. No influence of sex, age, or diet was observed on any form. Strong physical activity and anticipatory stress increased norepinephrine excretion and selectively increased MHPG glucuronide levels without changing the free or the sulfate excretion. We conclude that the total amounts of free, sulfate, and glucuronide MHPG found in urine originate from endogenous body pools with no interference of dietary components. The sympathetic nervous system seems to be the main source of glucuronide and arguments are given supporting the central origin of sulfate.

Eleven young students were tested to determine the relationship between the improvement of mental performances observed under prolonged submaximal work and central or peripheral catecholamine changes. The subjects pedaled a bicycle ergometer for 1 h at a work load individually calculated to approximate 75% of maximal oxygen uptake. The mental test, consisting of 1-h sessions of time-limited word tests and arithmetical calculations, required a high degree of concentration (vigilance and short-term memory). Catecholamines [epinephrine (E), norepinephrine (NE), dopamine (DA)], metanephrine (MN), normetanephrine (NMN) and the glucuronide conjugate of 3-methoxy 4-hydroxyphenylglycol (MHPG) were assayed in urine to assess peripheral activity: E and MN as indexes of adrenomedullary secretion, NE, NMN and MHPG glucuronide as markers of NE metabolism in sympathetic nerves. Urinary MHPG sulfate was determined as a possible marker of central noradrenergic metabolism. When compared to the effect of single tests, the combination of prolonged submaximal work and mental task induced significant increases in MHPG sulfate and E + MN excretions. Both these increases were correlated each to one another and also correlated to the number of discriminated words. Altogether, the present data show that prolonged submaximal work under mental load activates catecholamine systems and suggest that a relationship exists between adrenomedullary activation and the improvement of mental performance. Based on literature data, the possible modulatory role of peripheral E on mental processes and central noradrenergic activity is discussed.