Role of the carotid sinus nerve and of dopamine in the biochemical response of sympathetic tissues to long-term hypoxia.
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Adrenal Glands↗
Biomedical subjects
L Peyrin
Publications and source records attributed to L Peyrin.
Presence of chemosensitive SIF cells in the rat sympathetic ganglia: a biochemical, immunocytochemical and pharmacological study.
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Animals↗
Stimulatory effect of long-term hypoxia on the posterior part of A2 noradrenergic cell group in nucleus tractus solitarius of rat.
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Animals↗
[Biological diagnosis of pheochromocytoma: impact of technological improvement].
Laboratory diagnosis of pheochromocytoma must give evidence of increased catecholamine production. This requires measurement of catecholamines and their metabolites (normetanephrine NMN, metanephrine MN and/or VMA) in urine or in plasma. The various assays can be also performed during dynamic test that stimulate or inhibit catecholamine release. The recent introduction in biochemistry of high performance liquid chromatography coupled to electrochemical detection (HPLC-ED) has greatly reduced drug-induced interference and has therefore narrowed the reference value range. The two groups of compounds that have most benefited from such analytical improvements are urinary metanephrines and VMA. The technical progress has greatly simplified the laboratory diagnosis of pheochromocytoma both by improving the reliability of already available compounds and by favouring the development of news markers. However, the diagnostic sensitivity of the various urinary and plasmatic markers remains very unequal and the diagnosis of pheochromocytoma requires a carefully planned sequence of studies including appropriate biochemical tests able to affirm or to exclude the diagnosis with a high degree of security while reducing the duration and cost of the investigation. Among urinary markers, metanephrines remain the most direct indices of catecholamine hypersecretion and provide the most reliable biochemical indicators of the existence of pheochromocytoma. The diagnostic sensitivity of urinary metanephrines (about 98%) greatly exceeds that of catecholamines and VMA (60-70%). These differences are related to the diversity and specificity of physiological mechanisms involved in the synthesis, the release and inactivation of markers (catecholamines, metanephrines, VMA) and to the variety of clinical presentations and secretory patterns of pheochromocytomas. Considering the practical necessity of simplifying the collection of laboratory samples, use of plasma assays for the diagnosis of pheochromocytoma has become increasingly routine. However, plasma catecholamines--even when assayed during the clonidine suppression test--have not fully lived up to expectations. The diagnostic sensitivity is far better (about 98%) with the recently developed assays of plasma methoxyamines which, owing to their long half-life, provide long-lasting indicators of the catecholamine discharge and are elevated even in tumors without clinical expression. Laboratory diagnosis is relatively easy when the patient bears a large tumor releasing considerable amounts of catecholamines and metabolites; it becomes more challenging in the case of small tumors or of pretumoral hyperplasia in which only the most reliable biochemical markers are able to confirm the diagnosis of pheochromocytoma.
Adrenal Gland Neoplasms↗
Inter-relationships between pituitary-adrenal hormones and catecholamines during a 6-day Nordic ski race.
The aim of the study was to investigate the inter-relationships between pituitary-adrenal hormones and catecholamines during a prolonged competition over 6 days. Plasma adrenocorticotropic hormone (ACTH), cortisol (C), beta-endorphin (beta EP), free and sulphated adrenaline (A) and noradrenaline (NA) were measured in 11 volunteer male subjects during a national Nordic-ski race (323 km). Blood samples were obtained before the competition in the evening as control (D0), and before and after each day's racing (D1-D6). The mean daily heart rate (fc) was calculated from fc values recorded every minute during the race. The results showed the following: changes in mean fc [from 147 (SEM 3) to 156 (SEM 3) beats.min-1 according to the day] were not significant during the race. Diurnal variations in ACTH, beta EP and C were no longer apparent after the race: evening levels were higher than their respective D0 values during the race, except on D3 when there was a lack of response to exercise in the three hormones. Unlike ACTH and beta EP, pre- and postexercise C values on D1 and D2 were higher than those on the subsequent days (P less than 0.001). In contrast, there was a progressive accumulation of A and NA in pre- and postrace concentrations which reached a plateau in about 4 days. Positive correlations between exercise responses in ACTH, C and beta EP were found especially on D3 and D6 (P less than 0.001) but there were no significant correlations between catecholamines and the other three hormones. Thus, prolonged competition over 6 days evoked different control mechanisms for hormones of the pituitary-adrenal axis and catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Cortex Hormones↗
Differential effect of guanethidine on dopamine and norepinephrine in rat peripheral tissues.
The changes of dopamine (DA) and norepinephrine (NE) were investigated in rat peripheral tissues after guanethidine treatment (50 mg/kg i.p. five days each week) during one week (group 1, n = 10, five injections) and during 2.5 weeks (group 2, n = 8, 13 injections). Guanethidine greatly reduced NE levels in all the analyzed tissues but only partially depleted DA in kidney, bladder, stomach, intestine, lung and liver and in sympathetic ganglia. The differential pattern of changes between DA and NE induced by guanethidine suggests that peripheral DA is distributed in several neuronal or non-neuronal pools, whose presence, nature and contribution varies in the different tissues. Both noradrenergic cell bodies and small intensely fluorescent cells (SIF cells) can contribute to the DA in the superior cervical ganglion. Noradrenergic neurons seem to be the main sources of DA in seminal vesicles, vas deferens, heart and spleen. In addition to noradrenergic nerves, extraneuronal sources could account for a meaningful portion of DA in kidney, gastrointestinal tract, lung and liver. The bladder is the peripheral tissue where DA exhibits the highest resistance to the neurotoxin. Accordingly, these tissues may provide meaningful sources of non-precursor DA pools.
Animals↗
Malignant pheochromocytoma: a series of 14 cases observed between 1966 and 1990.
We report 14 patients (9 males, 5 females) aged 15-59 years, treated for malignant pheochromocytoma. These patients were observed during the 1966-1990 period along with 68 other patients presenting benign pheochromocytomas. From the initial general presentation of the 14 patients, two groups could be individualized. In seven patients, the initial presentation seemed benign. After the excision, the recovery was complete, but patients recurred on average 7.8 yr later (range 1-22 yr). Tumors were intraadrenal in six cases (5 single, 1 bilateral) and extraadrenal in one case. In the seven remaining patients, malignancy was evident from the first examination. The tumors were intraadrenal in 2 cases, extraadrenal in 5 cases. Frequency of extraadrenal locations (6/14) was in this series significantly higher than in benign forms (9/68). Diagnosis of malignancy was based on metastases in 12 cases (lymph nodes in 5, bones in 5, liver in 4, lung in 2, brain in 1) and on peritumoral extension in 2 cases. No biological specificity was detected in urinary excretion of catecholamines or its metabolites. In 6 patients so far studied, an uptake of 131I MIBG was found in the tumor and/or metastases. Four patients received therapeutic doses of 131I MIBG and in three of them, this treatment led to a good result within a follow-up range of 12 to 66 months.(ABSTRACT TRUNCATED AT 250 WORDS)
3-Iodobenzylguanidine↗
Response of noradrenaline and dopamine to hypoxia and sympathectomy: evidence for an independent dopaminergic reactivity.
In order to assess the status of dopamine in the periphery, we submitted rats to sympathectomy (with guanethidine), to hypoxia, and to both, and measured the concentration and turnover of noradrenaline and dopamine in peripheral organs. Sympathectomy decreased noradrenaline content by 96-99% in all the organs tested. In contrast, dopamine content, which was decreased by 90% in the heart, was not significantly changed in the bladder or lungs. Based on dopamine decrease after guanethidine, and on dopamine:noradrenaline ratios in organs, we conclude that in the heart the dopamine is contained mostly in noradrenergic terminals. In other organs it appears to be contained in non-noradrenergic structures. These are found in: the bladder, stomach, lungs, and kidneys, in decreasing importance. We estimated the turnover of noradrenaline by measuring the decrease of its concentration after inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine. Among the five organs studied, the turnover of noradrenaline was increased by long-term hypoxia (10% O2, 15 days) in the heart only (+140%). An increase of sympathetic activity during hypoxia was also found in the kidneys and lungs as shown by the increase in turnover of dopamine that was suppressed by sympathectomy. Hypoxia induced large increases in dopamine concentration in the stomach and the lungs (70 and 190% respectively). These increases were not abolished by sympathectomy and we propose that they are related to a chemosensory function of dopamine-containing paraganglia in the stomach and the lung.
Animals↗
The first breaths of air stimulate noradrenaline turnover in the brain of the newborn rat.
The aim of this study was to analyse the noradrenaline (NA)-turnover in the brain around birth and its significance for neonatal adaptation. NA and its metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) have been measured by high-pressure liquid chromatography (HPLC) in the pons-medulla and cortex in rat foetuses and pups. The MHPG/NA ratio was used as an index of NA-turnover. Catecholamines were also determined in the adrenals for comparison. The MHPG/NA ratios were found to increase 2.7-fold in the pons-medulla and 2-fold in the cortex during the first day after birth. The surge of NA-turnover occurred after the pups had been breathing air for two hours. The increase of NA-turnover was significantly lower in the cortex of rat pups breathing a hypoxic gas mixture or when they were kept in a cooler environment. The differences were less marked in the pons-medulla. We conclude that breathing air stimulates NA-turnover in the brain of the newborn rat and this stimulatory effect is modulated by environmental factors.
Animals↗
Differential effects of long-term hypoxia on norepinephrine turnover in brain stem cell groups.
The influence of long-term hypoxia on noradrenergic cell groups in the brain stem was assessed by estimating the changes in norepinephrine (NE) turnover in A1, A2 (subdivided into anterior and posterior parts), A5, and A6 groups in rats exposed to hypoxia (10% O2-90% N2) for 14 days. The NE turnover was decreased in A5 and A6 groups but failed to change significantly in A1. The NE turnover was increased in the posterior part of A2 and remained unaltered in the anterior part. In normoxic rats, the hypotensive drug dihydralazine induced a reverse effect, namely increased NE turnover in anterior A2 and no change in posterior A2. The neurochemical responses to hypoxia were abolished by transection of carotid sinus nerves. The results show that long-term hypoxia exerts differential effects on the noradrenergic cell groups located in the brain stem. Peripheral chemosensory inputs control the hypoxia-induced noradrenergic alterations. The A2 cell group displays a functional subdivision: the posterior part is influenced by peripheral chemosensory inputs, whereas the anterior part may be concerned with barosensitivity.
Animals↗
[Pheochromocytoma. Study of a personal series of 85 cases].
The study of a personal series of 85 cases observed by the same endocrinologist over a period of 40 years shows the modifications of clinical presentation and biological methods of diagnosis and treatment. There is a striking increase in the percentage of patients without any cardiac or vascular manifestations. The methoxyamines assay has the best sensitivity and specificity even in asymptomatic tumors. The recent development of this assay in the blood is very efficient. The tumor may be found with an abdominal CT scan. The use of NMR is not fruitful. The 131I MIBG scintigraphy is necessary if the CT scan is not informative and in malignant forms. The malignancy is more frequent (16.5%) than classical according to the long duration of the disease. The quite good prognosis is improved by the administration of 131I MIBG. The surgery was safer and without mortality over the last 15 years.
Adrenal Gland Neoplasms↗
Determination of free and conjugated normetanephrine and metanephrine in human plasma by high-performance liquid chromatography with electrochemical detection.
A simple method for the simultaneous assay of normetanephrine and metanephrine (both free and conjugated) in human plasma by high-performance liquid chromatography with electrochemical detection has been developed. The hydrolysed plasma is purified on a Dowex 50 H+ column, and the methoxylated amines are eluted with ammonia-methanol. The methoxyamines are assayed using a dual-series electrode arrangement with differential current measurement. This system greatly improves the assay specificity toward endogenous or exogenous metabolites and drugs. The high sensitivity of the method enables the determination in normal subjects of levels of normetanephrine and metanephrine.
Chromatography, High Pressure Liquid↗
Transection of carotid sinus nerve inhibits the turnover of dopamine and norepinephrine in long-term hypoxic carotid bodies: a biochemical and morphometric study.
To assess the efferent influence of the carotid sinus nerve on the catecholamine function and the vascularity in long-term hypoxic carotid bodies, rats were exposed to hypoxia (10% O2 in nitrogen for 1 and 3 weeks) after unilateral transection of the sinus nerve. In the intact carotid bodies, long-term hypoxia elicited several biochemical and morphological alterations: increased turnover of dopamine and norepinephrine, increased volume density of blood vessels, decreased volume density of glomic tissue. Transection of the sinus nerve reduced but did not abolish the increase in turnover of dopamine and norepinephrine evoked by hypoxia without preventing the structural alterations. Immunocytochemical studies revealed the presence of nerve fibres exhibiting neuropeptide Y-like immunoreactivity which persisted after the excision of the carotid sinus nerve. Nerve fibres showing substance P-like immunoreactivity were found in the intact carotid bodies but not in the carotid bodies deprived of sinus nerve. It is concluded that the sinus nerve exerts a stimulatory efferent control on the synthesis and release of dopamine and norepinephrine in rat carotid body during long-term hypoxia, but no appreciable vasodilatory influence on the glomic vasculature. A possible role of substance P contained in the endings of the carotid sinus nerve is discussed.
Animals↗
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↗
Effect of guanethidine on dopamine in small intensely fluorescent cells of the superior cervical ganglion of the rat.
To determine the portion of ganglionic dopamine stored in the small intensely fluorescent (SIF) cells of the superior cervical ganglion, rats were treated chronically with the neurotoxin guanethidine (50 mg/kg i.p. daily for 6, 13 or 18 days) which destroys noradrenergic neurons. The guanethidine effect was assessed in the ganglion using biochemistry of dopamine and norepinephrine and immunocytochemistry of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). After 18 days of treatment, the ganglionic norepinephrine content was reduced by 80%, but the dopamine content was reduced by only 20%. Morphologic analysis of ganglia stained to distinguish noradrenergic neurons (TH positive, DBH positive) and SIF cells (TH positive, DBH negative) indicated that guanethidine treatment reduced the number of noradrenergic neurons by 70%, dropping from 19413 +/- 1402 to 6515 +/- 1296 per ganglion, but increased the number of dopaminergic SIF cells by 80% from 578 +/- 150 to 1056 +/- 151 per ganglion. Based on these findings, it is concluded that a substantial portion of the dopamine in the rat superior cervical ganglion is located outside the noradrenergic neurons, i.e. in the SIF cells. Extrapolating the data obtained using guanethidine versus control rat leads to infer that although the proportion of SIF cells in the superior cervical ganglion is small (3 +/- 1% of the SIF and noradrenergic neurons combined), about 40% of the total ganglionic dopamine resides in SIF cells, with the remainder serving as precursor in noradrenergic neurons.
Animals↗
Plasma dopamine, norepinephrine, epinephrine and DOPAC levels in preterm infants prior to and immediately after a sleep ventilation hypercarbia test.
The postnatal maturation and the adaptational ability of the sympathoadrenal system has been investigated in preterm neonates (n = 8), and in sick preterm neonates with respiratory disorders (n = 10). Plasma levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and 3-4 dihydroxyphenylacetic acid (DOPAC) were evaluated at rest during the first month of life, and following an inhalation of a 5% carbon dioxide-21% oxygen mixture for 10 min. During the first month of life the sick preterm neonates exhibited similar NE, E, and DOPAC plasma levels but higher DA amounts than healthy infants. Plasma DA levels were inversely correlated with the transcutaneous oxygen tension (r = -0.636) indicating that hypoxemia was able to enhance the release of DA. Immediately following the hypercarbia test, there were no significant changes of plasma catecholamine levels in the sick preterms, but there was a significant increase of E plasma levels (+140%, p less than 0.05) and a moderate elevation of NE and DA amounts in the healthy preterms. It is concluded that preterm neonates who have had respiratory disorders did not exhibit an immaturity of the sympathoadrenal system at rest, but had a defect in the release of E following hypercarbia exposure, which may be secondary to an alteration in chemoreceptor function and/or reduced catecholamine stores.
3,4-Dihydroxyphenylacetic Acid↗
Measurement of plasma methoxyamines for the diagnosis of pheochromocytoma.
Urinary methoxyamine determination is considered as the most sensitive and specific parameter for the diagnosis of pheochromocytoma. Since blood sampling is easier to perform, we developed a new HPLC method to assay metanephrine (MN) and normetanephrine (NMN) in plasma. We now report the results for total (free and conjugated) MN and NMN in 22 cases of pheochromocytoma compared to 26 healthy subjects, 33 patients with essential hypertension, 14 with miscellaneous diseases and 4 patients with renal failure. The mean normal values (mean +/- SD) were 0.40 +/- 0.10 ng/ml for MN and 0.85 +/- 0.25 ng/ml for NMN. The sum of MN+NMN was 1.25 +/- 0.28 and the range 0.9-1.9. In essential hypertension, the range of NMN+MN was 1.2-6.0. In the 4 renal failures, both MN and NMN were drastically increased. In 49 samples drawn from 22 pheochromocytomas, MN was elevated over the hypertensive range in 34 samples and NMN in 47 samples. The total MN+NMN ranged from 6.2 to 436 ng/ml; this figure was observed whatever the clinical presentation even in silent tumors or in paroxysmal forms between the crisis. After tumor removal, the values dropped rapidly. In conclusion, plasma determination of MN and NMN provides a highly sensitive and specific biological pointer for the diagnosis of pheochromocytoma in patients without renal failure.
Adrenal Gland Neoplasms↗
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↗