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J M Pequignot

Publications and source records attributed to J M Pequignot.

At least 91 records · Page 5Linked to original sources

Preganglionic sympathetic fibres modulate dopamine turnover in rat carotid body during long-term hypoxia.

To assess the influence of sympathetic efferents on the dopamine function of carotid bodies, rats were exposed to long-term hypoxia (10% O2 in nitrogen for 1 or 3 weeks) after unilateral removal of the superior cervical ganglion. In the intact carotid bodies. long-term hypoxia increased the content and turnover of dopamine (DA). The dopaminergic response to hypoxia was reduced but not abolished by the ganglionectomy. To determine whether pre- or postganglionic sympathetic fibres are involved in the control of the dopamine function, rats were exposed to hypoxia either after unilateral transection of the preganglionic cervical trunk or after selective destruction of the postganglionic fibres by guanethidine. The preganglionic transection blunted the dopaminergic response to hypoxia whereas guanethidine had no effect. It is concluded that the sympathetic efferents may activate the synthesis and release of dopamine in glomus cells during long-term hypoxia. The sympathetic efferents responsible for the modulation of dopamine function are probably preganglionic fibres.

Animals↗

Plasma free and sulphated catecholamines after ultra-long exercise and recovery.

We investigated the early and late effects of two types of ultra-long exercise on sympatho-adrenal and dopaminergic activity. With this aim both free and sulphoconjugated plasma catecholamines (CA), noradrenaline (NA), adrenaline (A), and dopamine (DA) were determined in two groups of athletes immediately after completion of 24-h running or a 10-h triathlon and on recovery during the next 1-3 days. Both races stimulated the sympathetic activity, but differences were observed in the CA pattern: the 24-h run induced a marked elevation of free and sulphoconjugated NA (+175% and +180%, respectively) but failed to alter significantly A and DA levels. The triathlon challenge increased the three conjugated CA (NA sulphate +350%; A sulphate +110%; DA sulphate +270%) and to a lesser extent free CA (NA +45%; A +30%). On the first post-exercise morning, a sustained intense noradrenergic activity was still present in the 24 h-runners, as evidenced by the large increase in free and sulphated NA levels (+140% and +100%, respectively). Such a prolonged activity was also indicated after completion of the triathlon, by the increase of NA sulphate (+140%) observed on the 1st recovery day. However, after the triathlon there was a decreased release of A from the adrenal medulla for several days. These data show that both types of ultralong exercise are able to induce for several hours a sustained sympathetic activation during the test and in the recovery period. Furthermore, the study shows that plasma conjugated CA may provide delayed and cumulative indexes of sympathetic activation, complementary to the instantaneous markers such as free CA.

Catecholamines↗

Conjugation and deamination of circulating dopamine: relationship between sulfated and free dopamine in man.

In order to assess the importance of conjugation in dopamine metabolism, we infused dopamine (20 nmol/kg/min, 1 h) to seven male subjects, then measured the kinetics of free and conjugated dopamine and DOPAC (deaminated dopamine) in plasma both during and after the infusion. Dopamine increased as early as 2 min after the start of the infusion, then reached a plateau and remained elevated on a level of 25 times the basal value. Dopamine sulfate and DOPAC followed very similar patterns and increased continuously from the 30th and 20th min, respectively, until the end of the infusion (5.18- and 5.76-fold, respectively), but only dopamine sulfate remained elevated (1.65-fold) on the first day following infusion. DOPAC glucuronide increased moderately (2.58-fold) at the end of the experiment, but neither dopamine glucuronide nor DOPAC sulfate were increased despite high precursor circulating levels. Free DOPAC and dopamine sulfate levels during infusion were correlated with dopamine levels when all subjects were pooled. In addition, within a subject dopamine sulfate to dopamine correlations were found with slopes varying in a range of 1 to 15. Our results show that sulfation is significantly involved in the metabolism of circulating dopamine and is not easily saturated, suggesting that dopamine sulfate may be an index of endogenous dopamine release.

3,4-Dihydroxyphenylacetic Acid↗

Development of the arterial chemoreflex and turnover of carotid body catecholamines in the newborn rat.

1. The peripheral, arterial chemoreceptors in the carotid body are active and responsive in the fetus. At birth, when oxygenation increases, the chemoreceptors are silenced. Over the next few days the sensitivity is reset toward the adult level and the chemoreceptors influence breathing during normal conditions. In order to investigate the underlying mechanisms of this resetting we examined the strength of the chemoreflex in newborn rats and correlated this to the contents of dopamine and noradrenaline in the carotid bodies of the newborn pups and near-term fetuses. Furthermore, turnover rates of dopamine and noradrenaline were determined in newborn rats up to 1 week of age by analysis of catecholamine decreases after inhibition of synthesis with alpha-methyl-p-tyrosine. 2. Chemoreceptor influence was assessed by the method of 'physiological chemodenervation' with hyperoxia of 15-20 s duration in unanaesthetized rat pups. Relative changes in ventilation elicited by hyperoxia were determined by body plethysmography. We found no change in ventilation on the day of birth either in vaginally born rats or in near-term pups delivered by Caesarean section. After 1 day there was a significant decrease in ventilation of -19.4 +/- 2.3% (mean +/- S.E.M.) and at 7 days of age the decrease was -28.8 +/- 2.2%, suggesting an increasing influence from the peripheral chemoreceptors. 3. The contents of dopamine and noradrenaline were measured by high-performance liquid chromatography. Dopamine increased from 3.7 +/- 0.4 pmol (pair of carotid bodies)-1 in the fetus to a peak of 15.9 +/- 2.6, 6-12 h after birth followed by a decline to 7.1 +/- 0.7 at 7 days of age. Noradrenaline levels increased from 1.3 +/- 0.3 in the fetus to 9.6 +/- 1.1 pmol (pair of carotid bodies)-1 after 4 days. The turnover rate of dopamine decreased from 4.4 pmol (pair of carotid bodies)-1 h-1 0-6 h after birth to 1.0 at 6-12 h of age. The turnover rate of noradrenaline also decreased over the first hours following delivery. 4. Since dopamine is an inhibitory neuromodulator in this system, we suggest that the increase in sensitivity seen after the first day of life is, at least in part, due to a decrease in the release of dopamine and thus a removal of an inhibitory mechanism.

Animals↗

Catecholamines in the carotid body are unaffected by hypercapnia.

In contrast to the increased content of dopamine and norepinephrine in rat carotid body during hypoxia (10% O2 in nitrogen) for 3 and 21 days, hypercapnia (8% CO2 in air) for 21 days failed to alter the catecholamine concentrations. DOPAC content was elevated in hypoxia whereas there were no significant changes in hypercapnia. This finding supports the view that the mechanisms of peripheral chemoreception differ, at least partly, in hypoxia and hypercapnia.

3,4-Dihydroxyphenylacetic Acid↗

Catecholamines and fuels after an ultralong run: persistent changes after 24-h recovery.

This study examined the alterations induced by an ultralong distance run (169 +/- 6 km in 24 h) and by prolonged postrace recovery (24 h) on blood fuel metabolites and catecholamines in seven trained subjects. Ten minutes after the race, plasma concentrations of glycerol and free fatty acids (FFA) were decreased twofold. Plasma glucose was unchanged. Plasma concentrations of free norepinephrine (NE) and free dopamine (DA) increased from 2.73 +/- 0.28 to 5.41 +/- 1.11 nmol.l-1 and from 0.45 +/- 0.13 to 0.62 +/- 0.18 nmol.l-1 whereas free epinephrine (E) and insulin were unchanged; 24 h after the race, plasma glycerol and FFA concentrations remained elevated (twofold) and TG decreased twofold compared with resting levels. Concomitantly, plasma NE and DA levels remained elevated, respectively, 6.23 +/- 0.41 and 0.77 +/- 0.13 nmol.l-1. These data show that the alterations in circulating fuel metabolites and NE induced by the ultralong race were still present 24 h later. The involvement of lipid metabolism and catecholamines in processes of post-exercise recovery is discussed.

Adult↗

Sympathectomy provides evidence of dopamine storage in rat laryngeal nerve paraganglia.

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.

Animals↗

Body temperature and plasma prolactin and norepinephrine relationships during exercise in a warm environment: effect of dehydration.

The effects of euhydration (Eh) and light (Dh1) and moderate (Dh2) dehydrations on plasma prolactin (PRL) levels were studied in 5 young male volunteers at rest and during exercise to exhaustion (50% of VO2max) in a warm environment (Tdb = 35 degrees C, rh = 20-30%). Light and moderate dehydrations (loss of 1.1 and 1.8% body respectively) were obtained before exercise by controlled hyperthermia. Compared to Eh, time for exhaustion was reduced in Dh1 and Dh2 (p less than 0.01) and rectal temperature (Tre) rose faster in Dh2 (p less than 0.05). Both venous plasma PRL and norepinephrine (NE) increased during exercise at any hydration level (p less than 0.05). Plasma PRL reached higher values after 40 and 60 min in Dh2 and Dh1 (p less than 0.05). Plasma NE values were higher in Dh2 at rest and at the 40th min during exercise (p less than 0.05). Plasma PRL was linearly correlated to Tre and plasma NE (p less than 0.001) but unrelated to plasma volume variation and osmolality. Our results provide further evidence for the major effect of body temperature in exercise-induced PRL changes. Moreover, the plasma PRL-NE relationship suggests that these changes may result from central noradrenergic activation.

Adult↗

Long-term hypoxia increases the turnover of dopamine but not norepinephrine in rat sympathetic ganglia.

The content and turnover of dopamine, 3,4-dihydroxyphenylacetic acid and norepinephrine have been investigated in the superior cervical, coeliac and mesenteric ganglia of rats exposed to moderate normobaric hypoxia (10% O2 in N2) lasting for 2-28 days. the turnover was estimated by the decrease in amine contents after inhibition of catecholamine biosynthesis with alpha-methyl-p-tyrosine. In all 3 sympathetic ganglia, long-term hypoxia elicited a sustained increase in the content and turnover of dopamine. In contrast, the content and turnover of norepinephrine remained unchanged, except for a moderate increase in the coeliac ganglion after 14 and 28 days of hypoxia. These results suggest that the dopamine and norepinephrine pools in ganglia have a different functional significance and that rat sympathetic ganglia contain a pool of dopamine specifically sensitive to long-term hypoxia.

3,4-Dihydroxyphenylacetic Acid↗

Early hormonal effects of head-down tilt (-10 degrees) in humans.

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.

Adrenal Medulla↗

Relationships between catecholamine or 3-methoxy 4-hydroxy phenylglycol changes and the mental performance under submaximal exercise in man.

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.

Adult↗

Catecholamine content of cochlear and facial nerves. High-performance liquid chromatography analyses in normal and mutant mice.

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.

Animals↗

DL-propranolol inhibits the vascular changes in the rat carotid body induced by long-term hypoxia.

Two groups of rats were exposed to hypoxia (10% O2) for 1 and 3 weeks with or without daily injections of DL-propranolol (0.66 mg.kg-1 ip). The structure of the carotid body was analyzed by light microscopical morphometry and the catecholamine content was assayed by high performance liquid chromatography. Exposure to hypoxia induced enlargement of the carotid body due to enhanced vascularity and hypertrophy of glomic and interstitial tissues. The dopamine and norepinephrine content were increased at both 1 and 3 weeks of hypoxia and reached levels 40-50 times those of the controls. The DL-propranolol treatment abolished the vasodilatory effect of hypoxia within the first week but did not prevent the other structural changes or the rise in catecholamine content. The data suggest that 1. the vasodilation elicited by long-term hypoxia may be controlled by beta-adrenoceptors and 2. the structural and biochemical events occurring in rat carotid body during long-term hypoxia do not influence each other and thus seem to be controlled by different mechanisms.

Animals↗

Paraganglia of the rat recurrent laryngeal nerve after long-term hypoxia: a morphometric and biochemical study.

Paraganglia of the recurrent laryngeal nerve of rats exposed to hypoxia (10 +/- 0.5% O2) for 3 weeks became enlarged in volume by 2.6-fold. The volume densities of blood vessel lumen and endothelial cells were unchanged. The enlargement of the paraganglia was mainly attributed to hypertrophy of the dense-cored vesicle-containing cell. Concerning the profile diameter of the vesicle, a unimodal distribution of dense-cored vesicle cells was found in both control and hypoxic paraganglia. The vesicle diameter increased by about 19%, whereas the numerical density of dense-cored vesicles and the vesicle volume density were unaltered after hypoxia. Recurrent laryngeal nerves assayed by a sensitive high performance liquid chromatography technique contained an average of 1.9 pmol dopamine and 1.3 pmol norepinephrine. Exposure to 2 weeks of hypoxia increased the dopamine level to 4.9 pmol, whereas the norepinephrine content was unchanged. It is suggested from this study that the catecholamines determined are housed in the paraganglia of the recurrent laryngeal nerve.

Animals↗

Dopamine and norepinephrine dynamics in rat carotid body during long-term hypoxia.

The contents of dopamine (DA), norepinephrine (NE) and 3,4-dihydroxyphenylacetic acid (DOPAC), and the utilization rates (secretion plus breakdown) of DA and NE were measured in carotid bodies of rats exposed, to normobaric hypoxia (10% O2 + 90% N2) for 0, 2, 7, 14 or 28 days. Long-term hypoxia elicited gradual increase in DA, NE and DOPAC contents, which after 28 days were increased 27, 51 and 4.6 fold, respectively. The DA utilization rate estimated after blockade of biosynthesis by alpha-methyl-p-tyrosine gradually increased from two days to the end of hypoxic exposure. The utilization rate of NE was unaltered within the first 7 days but was greatly increased after 14 and 28 days. It was concluded that the utilization rates of both DA and NE were increased by long-term hypoxia but these increases had different time courses. Dopamine, whose utilization increased in the early stage of hypoxia, might exert neurochemical effects on the chemoreceptors throughout the exposure, whereas NE, whose utilization was stimulated after two weeks of hypoxia, might play a significant role only after a delay.

3,4-Dihydroxyphenylacetic Acid↗

Inhibitory effect of almitrine on dopaminergic activity of rat carotid body.

Almitrine increases ventilation by stimulating the peripheral arterial chemoreceptors. This study assessed the effects of acute and chronic almitrine treatments on the dopamine (DA) and norepinephrine (NE) contents and utilization rates in the rat carotid body. Almitrine (5 mg/kg ip) caused a 34% reduction in DA content after 30 min. Extending the almitrine treatment for 15 days (one daily ip injection) produced a further progressive diminution in DA stores (-55%; P less than 0.01). The utilization rate of DA measured after inhibiting catecholamine biosynthesis by alpha-methyl-p-tyrosine was strongly reduced by almitrine (-98% after 15 days; P less than 0.01). The effects of almitrine were dose dependent. The noradrenergic activity was much less altered by the drug. The data showed that almitrine can modify the dynamics of DA in rat carotid body producing a decrease in both content and utilization rate.

Almitrine↗