Biomedical subjects

J M Pequignot

Publications and source records attributed to J M Pequignot.

At least 109 records · Page 6Linked to original sources

PubMed1987

Sustained enhancement of the catecholamine dynamics in rat carotid bodies, adrenals, sympathetic ganglia and target organs under long-term moderate hypoxia.

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.

Adrenal Glands↗

PubMed1987

The antihypertensive drug DL-propranolol inhibits the vascular changes in rat carotid body during long-term hypoxia.

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.

Animals↗

PubMed1986

Biochemical evidence for norepinephrine stores outside the sympathetic nerves in rat carotid body.

Adult rats were submitted to pharmacological or surgical sympathectomy. The chronic administration of guanethidine caused tremendous reductions in the norepinephrine stores in heart and superior cervical ganglion due to the destruction of the sympathetic nerve fibers and cell bodies. Guanethidine-sympathectomy resulted in a 70% loss of norepinephrine in the carotid body, whereas the dopamine and DOPAC contents were unaltered. The surgical sympathectomy induced by removing the superior cervical ganglion led to similar results. The present data indicate that a considerable part of norepinephrine in the rat carotid body is stored in the sympathetic nerves. In addition, a significant part of norepinephrine resides outside the sympathetic nerves, probably within the glomus cells.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1986

Peripheral distribution of free dopamine and its metabolites in the rat.

Free dopamine (DA) and its metabolites, homovanillic acid (HVA) and 3-4 dihydroxyphenylacetic acid (DOPAC), have been measured and compared with norepinephrine (NE) concentrations in rat peripheral tissues using high performance liquid chromatography with electrochemical detection (HPLC-ED). Detectable amounts of DA and its metabolites were found in all the analyzed tissues. The highest levels were found in carotid body, sympathetic ganglia, urogenital tract and heart, the lowest in liver and lung. DA and DOPAC distribution was heterogeneous and unrelated to NE concentration. Both the variable value of the DA/DA+NE ratio and the presence of DA metabolites in peripheral tissues indicate that a portion of DA may be stored outside noradrenergic neurons and directly catabolized in specific DA pools.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1986

Catecholamines of endoneurial laryngeal paraganglia in the rat.

The catecholamines in the recurrent and superior laryngeal nerves of the rat were assayed by high performance liquid chromatography. The nerves were shown to contain high levels of dopamine (1.9 +/- 0.6 and 2.3 +/- 0.4 pmol, respectively) and noradrenaline (1.3 +/- 0.3 and 0.9 +/- 0.2 pmol, respectively). No adrenaline could be detected in any of the nerves. Reserpine markedly depleted the stores of these amines in both nerves. A significant increase in dopamine level was seen in the superior laryngeal nerve after treatment with a monoaminoxidase inhibitor, but not in the recurrent laryngeal nerve. The high levels of dopamine detected are presumably derived from endoneurial paraganglia which were demonstrated by glyoxylic acid-induced fluorescence. The source of noradrenaline is less evident, but noradrenaline is probably stored in both endoneurial paraganglia and in sympathetic nerve endings.

Animals↗

PubMed1985

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↗

PubMed1985

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↗

PubMed1985

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↗

PubMed1985

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↗

PubMed1984

Intact and sympathectomized carotid bodies of long-term hypoxic rats: a morphometric ultrastructural study.

The ultrastructure of the carotid body after exposure to hypoxia (10% O2) for one, two or three weeks was investigated morphometrically. The study was performed on rats after unilateral removal of the superior cervical ganglion. The normally occurring bimodal distribution of type I cells, representing cells with small vesicle profile diameters (SVC) and large vesicle profile diameters (LVC) respectively, changed after one week of hypoxia into a unimodal population. After one or two weeks of hypoxia the diameter range of dense-cored vesicle (DCV) profiles in type I cells was not different from that of DCV profiles in control LVC. After three weeks of hypoxia the DCV vesicle size was intermediate between those of control SVC and LVC. The volume density of DCV decreased after one week but returned to initial values after two and three weeks of hypoxia. At two or three weeks of hypoxia, however, the total cell volume was increased about 1.4 times which should reflect an increase of the total content of DCV at these times of exposure to hypoxia. An increased mean area of cell profiles indicates a hypertrophy of the type I cells, but no signs of hyperplasia could be detected. The ganglionectomy did not cause any remarkable changes compared to the intact carotid body except for a higher volume density of DCV during the early periods of hypoxia. It is inferred from the study that the increased total mass of type I cell tissue during long-term hypoxia is due to a hypertrophy of the cells. Furthermore, the type I cells can increase their storage capacity for catecholamines during hypoxia by an increase in the size and number of DCV.

Animals↗

PubMed1983

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↗

PubMed1983

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↗

PubMed1983

Intact and sympathectomized carotid bodies of long-term hypoxic rats. A morphometric light microscopical study.

Intact and sympathectomized carotid bodies from rats exposed to hypoxia (room-air mixed with N2 to a final oxygen concentration of 10%) for 1, 2 and 3 weeks were analyzed by morphometric methods using the light microscope. Exposure to hypoxia enlarges the carotid bodies, in which the vascularity increases dramatically from the first week. This changed vascularity seems to be due to enhanced vasodilatation. In addition, there is a pronounced profileration of the endothelial tissue, thus suggesting an ingrowth of new blood vessels. The volume density of glomic type I, and type II cells, decreases during hypoxia but when calculated in total volumes this entity is increased 3-fold. Sympathectomy does not modify the structural changes occurring during hypoxia when compared with carotid bodies with intact innervation. Though the primary elements in the mechanism of transduction in carotid body are unknown, a remodelling of the vascular architecture may be a method by which this chemoreceptor alters its sensitivity.

Animals↗

PubMed1980

Sex differences in the sympatho-adrenal response to isometric exercise.

The effects on heart rate, blood pressure, and plasma catecholamines (epinephrine, norepinephrine, dopamine) of sustained isometric contraction (SIC) were studied in six women and nine men. Each subject held a tension equivalent to 30% of maximal handgrip strength until exhaustion. There were no significant differences between women and men in the duration of handgrip. Rise of heart rate and blood pressure were similar for women and men. Considering the absolute plasma levels of each catecholamine, no sex differences was observed at rest and at any time during SIC, except for epinephrine whose concentration was higher in men at first min of SIC. On the other hand, women and men exhibited different adrenergic patterns in response to SIC: in the first min of exercise the plasma level of the three catecholamines increased in men whereas for women plasma catecholamines levels were essentially unaffected. Thus, epinephrine seems to play a minor role in the regulation of heart rate and blood pressure during SIC for women. Another interesting result of our study is that SIC is able to induce an increase in dopamine plasma level for women as well as for men.

Adult↗

PubMed1980

Catecholamine-fuel interrelationships during exercise in fasting men.

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.

Adrenal Medulla↗

PubMed1979

[Adrenergic response to intense muscular activity in sedentary subjects as a function of emotivity and training].

Seven male sedentary human subjects were studied during intense muscular work (80% of maximal oxygen uptake) performed either for 15 min or until exhaustion (mean duration: 47 +/- 2 min). Plasma catecholamines were estimated before and after the experiment by means of an original fluorimetric assay. Epinephrine or norepinephrine were individually isolated from plasma and assayed in single extracts by a highly sensitive fluorimetric method. Epinephrine and norepinephrine levels as low as 15 ng per liter were detectable by this procedure in human plasma. The adrenergic pattern was found to be greatly different from one subject to another and related to emotivity: the effect of this factor was revealed by the predominance of epinephrine in plasma at rest or under exercise (ratio NA/A less than 1). In nonemotive subjects (ratio NA/A greater than 1 at rest) plasma epinephrine and norepinephrine increased progressively during exercise. Increments after exercise were higher for norepinephrine changes; however, the fact that epinephrine concentrations correlated significantly with norepinephrine suggests a simulataneous and coordinated stimulation of adrenal glands and orthosympathetic nervous system. In emotive subjects (ratio NA/A less than 1 at rest) the apprehension of muscular work promoted a difference in catecholamine responses: norepinephrine release was not affected by subject's anxiety, while epinephrine secretion, already elevated before the test, reached a high degree of magnitude in the first minutes of muscular work, remaining nearly constant until exhaustion. Physical training of nonemotive subjects, during 2 months with two intense exercises by a week, reduced strongly norepinephrine release after exhaustive muscular work. In the same conditions, the adrenal-medullary response was not significantly modified when compared with untrained subjects. Our results suggest that the adrenergic behaviour during exercise is a function of effort intensity to be supplied; catecholamines seem to be important factors in regulating body homeostasy during muscular work in man. In addition, emotive subjects exhibit amplified adrenal-medullary response, which may be related to psychological stimuli.

Anxiety↗

PubMed1979

Metabolic adrenergic changes during submaximal exercise and in the recovery period in man.

The urinary excretion of dihydroxyphenylalanine (DOPA), catecholamines (CA) [dopamine (DA), norepinephrine (NE), and epinephrine (e)], their 3-O-methylated derivatives [3-O-methyldopamine (3-MT), normetanephrine (NMN), and metanephrine (MN)], and their deaminated metabolites [dihydroxyphenylacetic acid (DOPAC) and vanilmandelic acid (VMA)] was studied in six healthy men, at rest during short-term (15 min) or exhaustive submaximal exercise, and in the 2-h postexercise recovery period. During short-term exercise only NE and VMA excretions increased, whereas in postexercise period only DA output was enhanced. Exhaustive muscular work induced a rise in NE and E excretion during the test, and an increase in DA, NE, and NMN urinary levels during postexercise recovery, while the output of deaminated metabolites was unaltered. It is concluded that both release and synthesis of CA are stimulated by submaximal exercise, which induces, in addition to NE, a specific release of DA. A possible role of NE in lipid mobilization during recovery from exhaustive muscular work is evoked. The origin and role of released DA are also discussed.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1979

[Changes in blood levels of noradrenaline in man following short and long term exogenous infusion].

Norepinephrine (NE) was infused in four normal men in doses of 1.5, 6.0 and 9.0 microgram/min for 60 min. The rise in plasma NE was observed only after 5 min and steady state plasma NE and infusion rates. The calculated turnover time averaged 35 sec for 1.5 microgram/min infusion and 20 sec for both 6.0 and 9.0 microgram/min infusion experiments. These differences may be explained by adjustments occurring in inactivation processes in relation to infused doses. A basal endogenous overflow rate of 15 ng kg-1 min-1 was calculated for NE. In the month following NE infusion plasma concentrations decreased exponentially but remained above preinfusion values during about 10 days. The above results confirm the important role of inactivation mechanisms to remove NE from plasma and show that the amine taken up by sympathetic neurons may be released over a long period following the end of infusion.

Adult↗