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L Peyrin

Publications and source records attributed to L Peyrin.

At least 73 records · Page 4Linked to original sources

Comparative effect of tropolone and diosmin on venous COMT and sympathetic activity in rat.

The ability of diosmin to inhibit venous catechol-O-methyltransferase (COMT) activity was studied comparing it with tropolone in rat superior mesenteric vein (MV), inferior vena cava (IVC) and saphenous vein (SV). Diosmin inhibited COMT activity in the mesenteric vein after 200 and 400 mg/kg i.p., but only at 400 mg/kg in IVC. The COMT inhibitory effect of diosmin (400 mg/kg) was smaller than that of tropolone (50 mg/kg). Furthermore, diosmin, but not tropolone, increased urinary normetanephrine (NMN) excretion (+56%) at 400 mg/kg and that of 3-methoxy 4-hydroxyphenylglycol (MHPG) in a dose-dependent way, thus suggesting that diosmin may exert an activating effect on sympathetic activity. Both mechanism--local inhibition of COMT and enhanced sympathetic activity--may contribute to increase NE levels in the synaptic clefts of the vascular wall and explain the venoconstrictor effect of this drug.

Animals↗

The dynamics of dopamine metabolism in the rat superior cervical, coeliac and mesenteric ganglia.

Dopamine (DA) metabolism was compared in rat superior cervical ganglion, coeliac ganglion, mesenteric ganglion and adrenal medulla. Substantial amounts of DA, 3-4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were found in all the above structures. The proportion of DA metabolites over total adrenergic compounds increased from the superior cervical (22 +/- 2.2%) to the mesenteric ganglia (37 +/- 1.4%) and was much higher in ganglia (30 +/- 1.6%) than in adrenal medulla (1.1 +/- 0.3%). The turnover rates of DOPAC and HVA were calculated in sympathetic ganglia after pargyline (75 mg/kg i.p.) or probenecid (200-500 mg/kg i.p.). After pargyline, the DOPAC levels decreased faster than HVA levels in all ganglia. The corresponding half-lives and calculated turnover rates were: about 4 and 10 min and 100 and 40 pmol/mg protein per h for DOPAC and HVA respectively. No differences were observed between the three ganglia. After probenecid, DOPAC accumulated in all the ganglia in a dose-dependent way; HVA accumulated in the superior cervical and coeliac ganglia but not in the mesenteric ganglion. As in central areas, the turnover rates of DOPAC and HVA calculated on the basis of the greatest accumulation of acidic levels after probenecid were much smaller than those obtained after pargyline. Probenecid increased DOPAC levels in adrenal medulla, but the concomitant changes in DA and epinephrine (E) amounts suggest that probenecid was able to enhance adrenomedullary activity.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Sulfate and glucuronide conjugates of 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine of depressed patients: central and peripheral influences.

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 sub-groups suggests that as in normal subjects, central and peripheral NE activity are linked in depressed patients, but other factors may also modify sympathetic function. Taken together our data show that the separate assay of sulfate and glucuronide MHPG provides a better picture of NE dysfunction in depression than total MHPG measurement.

Adjustment Disorders↗

Effects of hypoxia on catecholamine and cardiorespiratory responses in exercising dogs.

The sympathoadrenal contribution to cardiorespiratory response elicited by hypoxia and/or exercise was assessed in the dog. The increased plasma norepinephrine (NE) and dopamine (DA) levels which follow hypoxia (fraction of inspired O2 equals 0.12) while epinephrine (E) remained unchanged ruled out the possibility of a primacy of the adrenal medulla in the response to hypoxia. In contrast to the lack of effect of hypoxic exposure, the adrenal medulla was substantially stimulated during exercise. The exercise-induced sympathoadrenal response remained unchanged during hypoxia as compared to normoxia when expressed as function of relative work intensity. Nevertheless at a given oxygen uptake, all plasma catecholamines were increased by hypoxia. These modifications in hormonal milieu failed, however, to alter the cardiac responses to exercise but were associated with a change in breathing pattern.

Animals↗

Epinephrine, norepinephrine, and dopamine during a 4-day head-down bed rest.

Head-down bed rest at an angle of 6 degrees was used as an experimental model to simulate the hemodynamic effects of microgravity, i.e., the shift of fluids from the lower to the upper part of the body. The sympathoadrenal activity during acute (from 0.5 to 10 h) and prolonged (4 days) head-down bed rest was assessed in eight healthy men (24 +/- 1 yr) by measuring epinephrine (E), norepinephrine (NE), dopamine (DA), and methoxylated metabolite levels in their plasma and urine. Catecholamine (CA) and methoxyamine levels were essentially unaltered at any time of bed rest. Maximal changes in plasma were on the second day (D2): NE, 547 +/- 84 vs. 384 +/- 55 pg/ml; DA, 192 +/- 32 vs. 141 +/- 16 pg/ml; NS. After 24 h of bed rest, heart rate decreased from 71 +/- 1 to 63 +/- 3/min (P less than 0.01). Daily dynamic leg exercise [50% maximum O2 uptake (VO2 max)] used as a countermeasure did not alter the pattern of plasma CA during bed rest but resulted in a higher urinary NE excretion during postexercise recovery (+45% on D2; P less than 0.05). The data indicate no evident relationship between sympathoadrenal function and stimulation of cardiopulmonary receptors or neuroendocrine changes induced by central hypervolemia during head-down bed rest.

Adult↗

Free dopamine in dog plasma: lack of relationship with sympathoadrenal activity.

To investigate the relationship between dopamine (DA) released into the bloodstream and sympathoadrenal activity, levels of free DA, norepinephrine (NE), and epinephrine (E) in plasma were recorded in four dogs subjected to three tests: treadmill exercise at two work levels [55 and 75% maximal O2 uptake; 15 min], normobaric hypoxia (12% O2; 1 h), combined exercise and hypoxia. Normoxic exercise induced slight nonsignificant decreases in the arterial partial pressure of O2 (PaO2), increases in NE [median values and ranges during submaximal work vs. rest: 1086 (457-1,637) vs. 360 (221-646) pg/ml; P less than 0.01] and E [277 (151-461) vs. 166 (95-257) pg/ml; P less than 0.05], but it failed to alter the DA level. Hypoxia elicited large decreases in PaO2 [hypoxia vs. normoxia: 42.8 (40.3-50.0) vs. 97.6 (83.2-117.6) Torr; P less than 0.01], increases in DA [230 (105-352) vs. 150 (85-229) pg/ml; P less than 0.01] and NE [383 (219-1,165) vs. 358 (210-784) pg/ml; P less than 0.05], but it failed to alter the E level. Combined exercise and hypoxia further increased NE levels but did not alter the DA response to hypoxia alone. The data indicate that free DA in plasma may vary independently of the sympathoadrenal activity.

Adrenal Medulla↗

Free, glucuronide, and sulfate catecholamines in the rat: effect of hypoxia.

The formation and excretion of conjugated catecholamines (CA) was studied in conscious rats after sympathetic stimulation by hypoxia (5.5-6% O2, 4 h). Hypoxia induced a rapid and intense increase of free epinephrine (E, X 12) and norepinephrine (NE, X 6) but only a limited enhancement of free dopamine (DA, X 2). Sulfate conjugates of E and NE had kinetics similar to the free forms, while glucuronides were only moderately and lately altered. In contrast to free and sulfated DA, DA glucuronide, the major plasma conjugate, was decreased (-25%). This result suggests that DA glucuronide, unlike other CA conjugates, is not related to detoxication but might supply a CA precursor. Urinary conjugates badly reflected plasma conjugates. In normoxic controls, CA conjugates prevailed in the plasma, whereas the free amines prevailed in the urine. Hypoxia increased mainly the excretion of E and NE glucuronide but not of the free amines. Urinary DA, free or conjugated, was decreased (-25%), a result in keeping with plasma DA glucuronide only. The poor relations between plasma and urine catecholamines pinpoint the importance of the kidney in CA handling.

3,4-Dihydroxyphenylacetic Acid↗

Studies on the central or peripheral origin of free and sulfated 3,4-dihydroxyphenylacetic acid in rat plasma.

The concentrations of free and sulfated 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in rat plasma to investigate their potential central or peripheral origin. Stimulation of central dopamine (DA) metabolism by a long-acting neuroleptic, pipotiazine (PPZ) selectively increased plasma levels of DOPAC sulfate whereas peripheral inhibition of monoamine oxidase by debrisoquin sulfate decreased free DOPAC levels only. These data suggest that the two forms of plasma DOPAC (free and sulfate) may have independent topographic origins. Peripheral DA pools seem to be the most likely sources for plasma free DOPAC whereas central dopaminergic neurons mainly contribute to plasma sulfated DOPAC. Our findings thus demonstrate that plasma DOPAC sulfate may be a useful indicator for central DA function in rat. Although further experiments are necessary to extrapolate our findings from rat to man, arguments are given indicating that measurements of plasma DOPAC sulfate might be of interest in human pathological and pharmacological investigations.

3,4-Dihydroxyphenylacetic Acid↗

Catecholamines and metabolic responses to submaximal exercise in untrained men and women.

The influence of exercise on blood borne substrates in relation to plasma catecholamine (CA) levels has been studied in untrained subjects (eight men and eight women). Subjects pedalled a bicycle ergometer for 20 min at a workload approximating to 80% maximal aerobic power. During exercise women reacted similarly to men except that their weight loss and hematocrit were significantly lower. At the end of the bicycling test, plasma dopamine (DA), norepinephrine (NE) and epinephrine (E) concentrations increased similarly in both groups. There was no significant difference in blood energy substrates between men and women except that the plasma free fatty acid (FFA) level was significantly higher in the female. When fitness levels were similar, the previously reported sex-related difference in response to exercise seemed to disappear. The lack of correlation between blood borne substrates variations and CA changes raised the question whether other hormonal factors combined with CA could play a role in the mobilization of energy substrates during exercise.

Adult↗

Free and conjugated 3-methoxy-4-hydroxyphenylglycol in human urine: peripheral origin of glucuronide.

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.

Adult↗

Glucuronide and sulfate catecholamine conjugates in rat and human plasma.

We have developed a method to selectively estimate free, glucuronidated and sulfated catecholamines (epinephrine [E], norepinephrine [NE], dopamine [DA]) in a single plasma sample. The method incorporates the first step of the catecholamine radioenzymatic assay and the selective enzymatic hydrolysis of conjugates by glucuronidase or sulfatase preparations. The method has been applied to rat and human plasma with a view to determine the relative importance of either conjugate (sulfate or glucuronide) toward free catecholamines. No previous reports were available for the concentration of either conjugate in rat plasma or the level of glucuronide conjugate in human plasma. Both sulfate and glucuronide conjugate of the three catecholamines were found in rat and human plasma, at different levels. Sulfate conjugates predominated in man and glucuronides in rat. In human, hand immersion in ice water for three minutes, which increased free catecholamine levels in the first minutes of the test, elicited too a delayed increase of glucuronide levels at the 30th minute (except for DA glucuronide which was already elevated at the third minute). As to the sulfates, only E sulfate was increased at the 10th minute. Our results suggest that glucuronidation may be an important pathway for catecholamine metabolism in man at rest or under sympathetic stimulation. In rat, our data point out the influence of blood sampling conditions (dietary, catheterization, decapitation) on the studied compounds and suggest that the nearest conditions from basal state may be fulfilled in sucrose-fed catheterized rats. The predominance of glucuronides in rat plasma agrees with previous metabolic reports.

Adult↗

[Strategy for the biochemical study of pheochromocytoma].

The measurement of urinary methoxyamines (metadrenaline and normetadrenaline) by a method as selective as possible, is the best test for the biochemical diagnosis of pheochromocytoma. Its diagnostic reliability (99,5 p. 100) is much higher than that of urinary catecholamines (59 p. 100) or VMA (38 p. 100) or plasma catecholamine measurement. Drug interference is reduced. Two or three tests on consecutive days are adequate to establish the diagnostic, even in intermittent secreting tumours.

Adrenal Gland Neoplasms↗

6-Hydroxydopamine lesions of dopaminergic A10 neurons. Long-term effects on the urinary excretion of free and conjugated catecholamines and their metabolites in the rat.

Free and conjugated catecholamines (dopamine, noradrenaline, adrenaline) and their methoxylated and/or deaminated metabolites were studied in rat urine after the bilateral destruction of the A10 dopaminergic cell group. Two months after the lesion, dopamine (DA) loss reached 91% in the nucleus accumbens, and was greater than 80% in olfactory tubercles, lateral septum and frontal cortex. At the same time urinary conjugated dihydroxyphenylacetic acid (DOPAC) was decreased by 45% whilst homovanillic acid (HVA) was increased only in its sulfated form (+62%). In contrast, no changes were observed in the free and conjugated forms of urinary DA, 3-methoxytyramine noradrenaline, normetanephrine, adrenaline, vanylmandelic acid, 3-methoxy-4-hydroxyphenylglycol and in the free forms of DOPAC and HVA. The present report confirms and extends our previous findings on the relationships between central dopaminergic activity and urinary deaminated metabolites of DA in the rat. It emphasizes the interest of urinary assays which could provide in vivo information on CNS functions.

3,4-Dihydroxyphenylacetic Acid↗

Conjugated HVA increase in rat urine after insulin-induced hypoglycemia: involvement of central dopaminergic structures but not of adrenal medulla.

To examine the possible contribution of Rat adrenal medulla to urinary DOPAC and HVA, we have studied these compounds in adrenals and urine under insulin-induced (5 IU/kg) hypoglycemic stimulation. In the urine samples collected over 16-hour-period following the intravenous insulin injection, there was a great increase in E, NE and their methoxylated derivatives MN and NMN, without change in DA, DOPAC, MHPG and free HVA excretion. In addition, there was a pronounced increase in urinary HVA conjugates (glucuronide and sulfate). Only very low amounts of DOPAC (10 +/- 2 ng/gland; 0.05% of catechols) and no detectable amounts of HVA (less than 3 ng/gland) were found in adrenal glands, without no significant change two hours after insulin, thus suggesting that Rat adrenal glands are not meaningful sources for urinary HVA and DOPAC. Since free HVA and total MHPG excretion remained unchanged, HVA contribution from sympathetic neurons seems unlikely in our study. In contrast, highly increased levels of conjugated HVA--and at a lesser extent of conjugated DOPAC--have been found in the striatum, which appears to be the most likely source of urinary HVA increment. The dopaminergic activation following insulin affected too the hypothalamus but not the nucleus accumbens. The role of such central dopaminergic activation has been discussed in terms of feeding behavior.

Adrenal Medulla↗

Sex-differences in catecholamine metabolites in human urine during development and at adulthood.

Adrenergic amines (dopamine [DA], norepinephrine [NE], epinephrine [E] and related compounds (DOPA, 3-methoxytyramine [MT], normetanephrine [NMN], metanephrine [MN], 3-5-dihydroxyphenylacetic acid [DOPAC], vanilmandelic acid [VMA] were analyzed in urine of human from one day to 40 years of age, in view to investigate the sex influence on catecholamine metabolism during life. In neonatal life (1 day to 3.5 months), the total amounts of urinary (E + MN) and (NE + NMN + VMA) were lower in girls than in boys, the former two compounds being mainly of adrenal medullary origin and the latter three coming largely from the sympathetic neurons. In adulthood, women excreted epinephrine (12.5 +/- 2.2 micrograms/24 hours) at lower levels then men (22.8 +/- 4.5 micrograms/24 hours) but no sex related differences occurred in the total amounts of urinary E + MN and NE + NMN + VMA. It is concluded from our study that, during the neonatal life, girls exhibit a lesser adreno-sympathetic maturity than boys, but full maturation of peripheral adrenergic sites is reached near to the fifth year of age in both sexes. The role of testosterone has been discussed. In adults, the lower epinephrine levels found in women urine do not seem to result from a sex difference in the degree of adrenergic maturity, but perhaps partly from an increased rate of epinephrine inactivation by catechol-O-methyltransferase.

Adolescent↗

Free and conjugated catecholamines and metabolites in cat urine after hypoxia.

Catecholamine and metabolite excretion was studied in the cat after 6 h of 7.5% O2 hypoxia. Norepinephrine (NE) release from sympathetic nervous endings was strongly activated, whereas epinephrine (E) excretion was only slightly increased. A noteworthy result was the increase of dopamine (DA) and its metabolites [3-methoxytyramine (MT); 3,4-dihydroxyphenylacetic acid (DOPAC)] in urine samples. This increased release does not seem to originate from the central nervous system, but rather from peripheral dopaminergic structures; available knowledge on peripheral DA suggests that the hypoxia-induced DA release might be partly related to chemosensory or renal function. Indeed, in addition to enhanced DA and NE excretion, we observed an increase in sodium excretion that correlated with both DA and NE. Analysis of free and conjugated urinary metabolites showed that only free NE and both free and conjugated normetanephrine were increased in urine after hypoxic stress. Among DA metabolites, conjugated DOPAC was the main DA metabolite in the basal state and after hypoxia. Both the free and the conjugated forms of DA, MT, and DOPAC were increased by hypoxia.

Adrenal Medulla↗

Urinary excretion of catecholamines in the night monkey (Aotus trivirgatus) (Primates, Cebidae).

A seasonal variation in the urinary catecholamines output has been demonstrated in two simians kept under constant ambient conditions : the nocturnal Aotus and the diurnal Saïmiri sciureus. In Aotus, catecholamines output (NA + A), in spring, is higher than in other Primates including man and even more so in winter. Cold exposure increases the NA + A excretion in Aotus as it does in squirrel monkey and rat but the A output is particularly prominent in Saïmiri. Fasting does not alter significantly the catecholamines excretion. Associated fasting and cold exposure do not modify the adrenosympathetic response observed in Aotus in cold conditions alone, but depresses the sympathetic activity and greatly enhance the adrenomedullary excretion in squirrel monkey, as it is the case in rat. Associated fasting and cold represents a highly stressful situation for squirrel monkey but not for night monkey. Catecholamines metabolites (MN, NMN, DOPAC, HVA, VMA and MHPG) are found in urine of both species, DOPAC and VMA being predominant in Aotus but DOPAC and MHPG in Saïmiri. The proportions of conjugated forms vary according to the metabolite : DOPAC and VMA are mainly under free form but NMN, MN and MHPG are mostly conjugated in both species. The daily output of pooled adrenergic metabolites (expressed as ng/mg creatinine) is higher in Aotus than in Saïmiri and man. Both monkey species display a high adrenosympathetic activity which does not correlate with their resting metabolic rate.

Animals↗