Jean-Marie Cottet-Emard

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

SummaryWe 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 24h-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.

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.

Sympathetic stimulation induced by hand cooling alters cold-induced vasodilatation in humans.

Abstract Hand cooling is a cold pressor test, which induces general sympathetic stimulation. This cooling procedure is often performed to investigate cold induced vasodilatation (CIVD) in one finger. To investigate the effects of this sympathetic stimulation on local CIVD, 12 subjects immersed either the right index finger (T1), right hand (T2) or left hand and right index finger (T3) for 30 min in water at 5°C followed by 15-min recovery. Skin temperature and skin blood flow (Q˙sk) measured by laser Doppler flowmetry on the right index finger, as well as heart rate (fc) and mean arterial blood pressure (), were continuously monitored during the three tests. Cutaneous vascular conductance was calculated as Q˙sk/. Concentrations of plasma noradrenaline (NA) and adrenaline (AD) were measured at different times during the tests. The results showed no cardiovascular change in T1, whereas fc and increased significantly at the beginning of both T2 and T3. Similarly, sympathetic stimulation was reflected in the NA concentrations, which increased significantly (P < 0.01) during T2 and T3 after 5 min of immersion, and remained elevated until the recovery period. The AD concentration did not change during the three tests. During T2, the CIVD appeared later and slower in comparison with T1 [CIVD onset: 12.81 (SEM 2.30) min in T2 and 5.62 (SEM 0.33) min in T1] . During T3, the CIVD onset was not delayed compared to T1 [6.38 (SEM 0.67) min], but the rewarming was lower [+5.40 (SEM 0.86)°C in T3 and +9.10 (SEM 1.31)°C in T1]. These results showed that CIVD could be altered by sympathetic stimulation but it also appeared that the onset of CIVD could be influenced by local cooling, independently of the general sympathetic stimulation.

Effects of hydration state on hormonal and renal responses during moderate exercise in the heat

Abstract The effects of hydromineral hormones and catecholamines on renal concentrating ability at different hydration states were examined in five male volunteers while they performed three trials. Each of these trials comprised a 60-min exercise bout on a treadmill (at 50% of maximal oxygen uptake) in a warm environment (dry bulb temperature, 35°C; relative humidity, 20–30%). In one session, subjects were euhydrated before exercise (C). In the two other sessions, after thermal dehydration (loss of 3% body mass) which markedly reduced plasma volume (PV) and increased plasma osmolality (osmpl), the subjects exercised either not rehydrated (Dh) or rehydrated (Rh) by drinking 600 ml of mineral water before and 40 min after the onset of exercise. During exercise in the Dh compared to C state, plasma renin, aldosterone, arginine vasopressin (AVP), noradrenaline and adrenaline concentrations were increased (P < 0.05). A reduction in creatinine clearance and urine flow was also observed (P < 0.05) together with a decrease in urine osmolality, osmolar clearance and sodium excretion, while free water clearance increased (P < 0.05). However, compared to Dh, Rh partially restored PV and osmpl and induced a marked reduction in the time courses of both the plasma AVP and catecholamine responses (P < 0.05). Values for renal water and electrolyte excretion were intermediate between those of Dh and C. Plasma atrial natriuretic peptide presented similar changes whatever the hydration state. These results demonstrate that during moderate exercise in the heat, renal concentrating ability is paradoxically reduced by prior dehydration in spite of high plasma AVP levels, and might be the result of marked activation of the sympatho-adrenal system. Rehydration, by reducing this activation, could partially restore the renal concentrating ability despite the lowered plasma AVP.

Changes in the sympathetic nervous system induced by 42 days of head-down bed rest

Changes in autonomic nervous system activity could be linked to the orthostatic intolerance (OI) that individuals suffer after a spaceflight or head-down bed rest (HDBR). We examined this possibility by assessing the sympathetic nervous system activity during 42 days of HDBR in seven healthy men. Heart rate variability was studied with the use of power spectral analysis, which provided indicators of the sympathetic (SNSi) and parasympathetic (PNSi) nervous system influences on the heart. Urinary catecholamines and the spontaneous baroreflex sensitivity were measured. Urinary catecholamines decreased by 21.3%, showing a decrease in SNSi. Heart rate variability was greatly reduced during 42 days of HDBR with a drop in PNSi but with no significant changes in SNSi. The baroreflex sensitivity was greatly reduced (30.7%) on day 42 of HDBR. These results suggest a dissociation between the catecholamine response and the SNSi of the heart rate. This dissociation could be the consequence of an increase in beta-adrenergic receptor density and/or activity induced by a decrease in catecholamines during HDBR. The subjects who suffered from OI also had a greater sympathetic response and much lower baroreflex sensitivity when supine than those who finished the stand test. However, the mean response of all subjects indicated that the sympathetic activity (catecholamine excretion) was probably slightly inhibited during HDBR and could contribute to OI.

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.

Specific sound-induced noradrenergic and serotonergic activation in central auditory structures

We have studied the noradrenergic and serotonergic changes induced by white noise stimulation at 70, 90 or 110 dB SPL for 45 min, in cochlear nuclei, inferior colliculus (IC), primary auditory cortex (PAC) and as a comparison in locus coeruleus (LC) and raphe dorsalis using HPLC. Both noradrenergic and serotonergic pathways were activated in the dorsal+posteroventral cochlear nuclei (DCN+PVCN) without changes in the anteroventral cochlear nucleus (AVCN) and IC. In the DCN+PVCN the noradrenergic activation was restricted to animals exposed to 70 dB SPL whereas the increase of serotonin content was intensity-dependent. In PAC serotonergic activation was observed only after 70 dB SPL exposure. These data suggest that in physiological conditions (70 dB SPL) noradrenergic and serotonergic regulation of the processing of auditory information occurs specifically in the dorsal cochlear nucleus where the control of incoming information to higher auditory structures takes place (i.e. IC and PAC). We suggest that the serotonergic activation in the primary auditory cortex for 70 dB SPL sound stimulation could be related to the fact that low-intensity white noise stimulation could be the most plastic-demanding processing in the auditory cortex.

Aging effects on monoamines in rat medial vestibular and cochlear nuclei

Noradrenaline (NA), dopamine (DA); serotonin (5-HT) and their metabolites-3-methoxy, 4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA)-were determined using HPLC in medial vestibular nucleus (MVN), anteroventral cochlear nucleus (AVCN), dorsal+posteroventral cochlear nucleus (DCN+PVCN), locus coeruleus (LC) and raphe dorsalis of Dark Agouti-Hanovre (DA-HAN) rats aged 4, 21 and 24 months. In older rats, the main noradrenergic changes were a decrease of NA content with an increase of the MHPG/NA ratio in MVN and a selective NA increase in AVCN. 5-HT and 5-HIAA levels were increased in all the brainstem nuclei except raphe dorsalis. DA and DOPAC remained unchanged. These data show that noradrenergic neurons in sensory nuclei are differently affected by aging whereas serotonergic activation occurs in most of them possibly as a compensatory response to dysfunction of sensory input and processing. The increase of NA stores in the AVCN of aged rats is in line with the elevated auditory brainstem threshold reported in old rats and could improve the signal-to-noise ratio. Noradrenergic neurons in the MVN seem to be more sensitive to age effect than cochlear nuclei; however, even if neuronal loss occurs, NA synthesis and/or metabolism increase to ensure normal or increased noradrenergic activity.

Long-term exposure to ozone alters peripheral and central catecholamine activity in rats

Abstract In addition to its noxious influence on lung airways, ozone inhalation can induce extrapulmonary neural dysfunctions the mechanisms of which are poorly understood. This study was intended to characterize the effects of long-term exposure to ozone (0.5 ppm, 5 days) on catecholamine activity in rat sympathetic efferents and brain areas of prime importance to adaptation to environmental stressors. Catecholamine activity was assessed by estimating the turnover rate of catecholamines and in vivo tyrosine hydroxylase activity in peripheral and central structures, i.e., heart, lungs, superior cervical ganglia, cerebral cortex, hypothalamus and striatum, A2 cell group within the nucleus tractus solitarius (NTS), and locus ceruleus (A6). Ozone inhibited norepinephrine turnover in heart (–48% of the control level) but not in lungs. Ozone failed to modify the tyrosine hydroxylase activity in superior cervical ganglia, and the catecholamine content in the adrenal glands. In the central nervous system, ozone inhibited tyrosine hydroxylase activity in noradrenergic brainstem cell groups, including the locus ceruleus (–62%) and the caudal A2 subset (–57%). Catecholamine turnover was decreased by ozone in the cortex (–49%) and striatum (–18%) but not in the hypothalamus. The data show that ozone can produce marked neural disturbances in structures involved in the integration of chemosensory inputs, arousal, and motor control.

Long-term prenatal hypoxia alters maturation of adrenal medulla in rat.

Catecholamine release from the adrenal medulla glands plays a vital role in postnatal adaptation. A number of pathologic situations are characterized by oxygen deficiency. The objective of the present study was to determine the influence of long-term prenatal hypoxia on maturation of the adrenal medulla. Pregnant rats were subjected to hypoxia (10% O2) from the fifth to the 20th d of gestation. The offspring were examined on the 19th d of gestation (E19), the day of birth (P0), and at postnatal (P) day of life P3, P7, P14, P21, and P68. The catecholamine content and activity of tyrosine hydroxylase (TH) in vivo were assayed by HPLC with electrochemical detection. Cellular expression of TH and phenylethanolamine N-methyl transferase was evaluated by protein immunohistochemistry and in situ hybridization of the corresponding mRNA species. Exposure to prenatal hypoxia reduced the epinephrine content of the adrenal medulla on E19, P0, P3, and P7 while increasing the norepinephrine content on E19, P0, and P14. Furthermore, the peak epinephrine to norepinephrine ratio appearing between P7 and P10 in the normoxic offspring was absent in the hypoxic offspring. The in vivo TH activity was increased on P3 and P14 and decreased on P68. The percentage of chromaffin cells in the medulla expressing TH and phenylethanolamine N-methyl transferase was lowered on E19, P0, and P7. TH and phenylethanolamine N-methyl transferase mRNA levels were reduced on P7. Clearly prenatal hypoxia results in major changes in adrenal catecholamine stores and synthesis during the perinatal period, which persist into adulthood. The capacity to cope with postnatal stress might be disturbed as a consequence of prenatal hypoxia.