Neurochemical reorganization of O2 chemoreflex pathway after carotid body denervation in rats.
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Animals↗
Biomedical subjects
J M Pequignot
Publications and source records attributed to J M Pequignot.
Sympathetic stimulation induced by hand cooling alters cold-induced vasodilatation in humans.
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 degrees 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 (f(c)) and mean arterial blood pressure (BP(a)), were continuously monitored during the three tests. Cutaneous vascular conductance was calculated as Q(sk)/(BP(a)). 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 f(c) and (BP(a)) 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) degrees C in T3 and +9.10 (SEM 1.31) degrees 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.
Adult↗
Involvement of the catecholaminergic system in glucagon-induced thermogenesis in Muscovy ducklings (Cairina moschata).
Physiological studies have shown that glucagon is a potential mediator of nonshivering thermogenesis (NST) in birds. The present work was undertaken in order to investigate whether the observed thermogenesis results from a direct action of glucagon on avian thermoregulatory mechanisms or in fact requires the participation of other agents such as catecholamines. Our experiments were performed using cold-acclimated (CA) ducklings which developed muscle NST. A comparison was made with thermoneutral (TN) ducklings of the same age. Our principal results showed that: (1) at ambient temperature (25 degrees C), circulating norepinephrine (NE) was markedly decreased in CA ducklings (-42%), while circulating epinephrine (E) did not undergo any consistent change; (2) in CA and TN ducklings, an intraperitoneal injection of glucagon (360 microg x kg(-1)) was followed after 10 min by prominent lipolysis and a large increase in circulating NE (4- to 6-fold) and E (14- to 17-fold), which was sustained for at least 1 h. The elevation of circulating NE was less pronounced in CA ducklings. The thermogenic action of glucagon in birds is probably indirect and involves at least the mobilization of lipids and sympatho-adrenal stimulation. The changes in peripheral noradrenergic activity during cold acclimation could be associated with adaptive changes leading to NST.
Acclimatization↗
Spinal cord monoaminergic system response to age and cold-acclimatization in muscovy duckling.
The effect of age and cold acclimatization on the regional distribution of monoamines in duckling spinal cord was studied. In thermoneutral controls (TN), the high dopamine (DA) to norepinephrine (NE) ratios (0.25 at 4 weeks of age and 0.15 at 6 weeks of age) suggest the presence of specific (non precursor) dopaminergic pools in cervical spinal cord. DA levels and the ratio of DA to NE were lowered by age and cold exposure in the cervical cord. In TN ducklings, serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) showed a decline with age in the spinal cord, indicating that this system is affected with development, whereas cold exposure prevents this decrease. The contents of 5-HT (+58%), 5-HIAA (+93%) and the ratio of 5-HIAA to 5-HT (+50%) are higher in the cervical spinal cord of cold acclimated than in TN ducklings. These results indicate that central monoaminergic systems are markedly affected by age and cold exposure.
3,4-Dihydroxyphenylacetic Acid↗
Effects of intracerebroventricular injections of des-His1 (Glu9) glucagon amide on the regulatory thermogenesis in muscovy ducklings.
Recent investigations have demonstrated a modulatory action of glucagon on shivering via the central nervous system in ducklings. Such an action could be mediated by glucagon receptors that have been recently detected in several brain areas involved in the central control of the involuntary motricity in this avian species. The present study using des-His1 (Glu9) glucagon amide, was performed to investigate the central mechanisms of glucagon on shivering. This glucagon analog was found to be an antagonist of glucagon devoid of adenylate cyclase activity (GR2) by triggering the breakdown of inositol phosphate (GR1) in mammals hepatocytes. The intracerebroventricular administration of des-His1 (Glu9) glucagon amide or glucagon induced a marked inhibition of shivering in ducklings exposed to cold. It seems likely that GR1 receptors contribute to decreased shivering in ducklings exposed to cold. Central glucagon or des-His1 (Glu9) glucagon amide were devoid of thermogenic effect at thermoneutrality.
Animals↗
O2-sensing after carotid chemodenervation: hypoxic ventilatory responsiveness and upregulation of tyrosine hydroxylase mRNA in brainstem catecholaminergic cells.
Ventilatory responses to acute and long-term hypoxia are classically triggered by carotid chemoreceptors. The chemosensory inputs are carried within the carotid sinus nerve to the nucleus tractus solitarius and the brainstem respiratory centres. To investigate whether hypoxia acts directly on brainstem neurons or secondarily via carotid body inputs, we tested the ventilatory responses to acute and long-term hypoxia in rats with bilaterally transected carotid sinus nerves and in sham-operated rats. Because brainstem catecholaminergic neurons are part of the chemoreflex pathway, the ventilatory response to hypoxia was studied in association with the expression of tyrosine hydroxylase (TH). TH mRNA levels were assessed in the brainstem by in situ hybridization and hypoxic ventilatory responses were measured in vivo by plethysmography. After long-term hypoxia, TH mRNA levels in the nucleus tractus solitarius and ventrolateral medulla increased similarly in chemodenervated and sham-operated rats. Ventilatory acclimatization to hypoxia developed in chemodenervated rats, but to a lesser extent than in sham-operated rats. Ventilatory response to acute hypoxia, which was initially low in chemodenervated rats, was fully restored within 21 days in long-term hypoxic rats, as well as in normoxic animals which do not overexpress TH. Therefore, activation of brainstem catecholaminergic neurons and ventilatory adjustments to hypoxia occurred independently of carotid chemosensory inputs. O2-sensing mechanisms unmasked by carotid chemodenervation triggered two ventilatory adjustments: (i) a partial acclimatization to long-term hypoxia associated with TH upregulation; (ii) a complete restoration of acute hypoxic responsivity independent of TH upregulation.
Adaptation, Physiological↗
Gender differentiation of the chemoreflex during growth at high altitude: functional and neurochemical studies.
The effect of chronic hypoxia on gender differences in physiology and neurochemistry of chemosensory pathways was studied in prepubertal and adult rats living at sea level (SL; Lyon, France) or at high altitude (HA; La Paz, Bolivia, 3,600 m). HA adult rats had higher hematocrit (Ht%), Hb concentration, resting ventilatory rate (Ve(100)), and higher tyrosine hydroxylase (TH) activity in carotid bodies (CB) than SL animals. At HA and SL, adult females had lower Ht% (46.0 +/- 0.8 vs. 50.4 +/- 0.6% at HA, P < 0.05 and 43.8 +/- 0.9 vs. 47.1 +/- 0.8% at SL, P < 0.05) and Hb (16.1 +/- 0.3 vs. 17.7 +/- 0.2 g/dl at HA, P < 0.05 and 14.5 +/- 0.3 vs. 15.6 +/- 0.1 g/dl at SL, P < 0.05) than males. Females had higher Ve(100) [170 +/- 19 vs. 109 +/- 7 ml. min(-1). 100 g(-1) at HA, P < 0.05 and 50 +/- 3 vs. 40 +/- 2 ml. min(-1). 100 g(-1) at SL, not significant (NS)] and lower CB-TH activity (1.40 +/- 0.2 vs. 3.87 +/- 0.6 pmol/20 min at HA, P < 0.05 and 0.52 +/- 0.1 vs. 0.68 +/- 0.1 pmol/20 min at SL; NS) than males at HA only. The onset of hypoxic ventilatory response during development was delayed at HA. Prepubertal HA females had higher Ve(100) than males (2 wk old, +47%) and higher CB-TH activity (3 wk old, +51%). Medullary noradrenergic groups were sex dimorphic during development at SL. Rats raised at HA had a drop of TH activity between the second and the third postnatal week in all medullary groups. In conclusion, our data support the hypothesis that the CB is the major site for sexual differentiation of the ventilatory control. Ventilatory differences appeared before puberty, and the animals bred at HA had profound alterations in the developmental process of the chemoreflex and its neural pathways. Some of these alterations are under dependence of the sex of the animal, and there is an important interaction between gender and the hypoxic environmental condition during the developmental period.
Age Factors↗
Plasticity in the phenotypic expression of catecholamines and vasoactive intestinal peptide in adult rat superior cervical and stellate ganglia after long-term hypoxia in vivo.
Sympathetic ganglia in the adult rat contain various populations of nerve cells which demonstrate plasticity with respect to their transmitter phenotype. The plasticity of the neuronal cell bodies and of the small intensely fluorescent cells in the superior cervical and stellate ganglia in response to hypoxia in vivo (10% O2 for seven days) was assessed by studying the expression of catecholamines and vasoactive intestinal peptide. The levels of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid and vasoactive intestinal peptide immunoreactivity were determined. In addition, the density of the immunohistochemical staining of cells for tyrosine hydroxylase and vasoactive intestinal peptide was evaluated. In the intact superior cervical ganglion, hypoxia increased the dopamine level as well as the density of small intensely fluorescent cells immunolabelled for tyrosine hydroxylase and vasoactive intestinal peptide. In the axotomized ganglion, hypoxia elicited a twofold rise in the level of the vasoactive intestinal peptide as well as enhancing the density of neuronal cell bodies immunostained for this peptide. Thus, the effect of hypoxia on the expression of vasoactive intestinal peptide expression in neurons was dependent on neural interactions. In the intact stellate ganglion, hypoxia alone induced a 1.5-fold increase in the density of neuronal cell bodies immunostained for vasoactive intestinal peptide. Thus, ganglia-specific factors appeared to play a role in determining changes in neuronal phenotype in response to hypoxia. The present study provides evidence for the involvement of dopamine and vasoactive intestinal peptide in ganglionic responses to long-term hypoxia as well as for differential responses by the two ganglionic cell populations, i.e. neuronal cell bodies and small intensely fluorescent cells. Changes in the expression of the vasoactive intestinal peptide during long-term hypoxia may be of energetic, trophic and/or synaptic significance. Hypoxia may be considered to be a vasoactive intestinal peptide-inducing factor in sympathetic ganglia.
Animals↗
Altered daily rhythms of brain and pituitary indolamines and neuropeptides in long-term hypoxic rats.
To determine whether sustained hypoxia alters daily rhythms in brain and pituitary neurotransmitters, the daily variations in vasoactive intestinal peptide-like immunoreactivity (VIP-LI), neuropeptide Y-like immunoreactivity (NPY-LI), serotonin (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) content were determined in discrete brain regions, pineal gland and anterior pituitary of hypoxic (10% O(2); 14 days) and normoxic rats. Hypoxia suppressed daily variations in VIP-LI in the suprachiasmatic nuclei (SCN) and the anterior pituitary, enhanced the daily rhythmicity in serotonergic elements of the caudal part of the dorsomedial medulla oblongata (DMMc), and even induced daily variations in NPY-LI in the DMMc as well as in the ventrolateral medulla oblongata. In addition, punctual alterations in the rhythmicity of 5-HT and 5-HIAA in the pineal gland and of plasma corticosterone were observed in hypoxic rats. Thus results of this study indicate that a permanent nonphotic stimulus, such as sustained hypoxia, may affect the functioning of the internal clock located in the SCN and may alter the daily rhythmicity in neurotransmitter content of some brain nuclei and the pituitary gland.
Animals↗
Dexamethasone's influence on tyrosine hydroxylase activity in the chemoreflex pathway and on the hypoxic ventilatory response.
Catecholamines have been implicated in neuromodulation of peripheral chemosensitivity and central respiratory mechanisms. Because glucocorticoids can affect catecholamine metabolism in the carotid body and brainstem, this study explored the possibility that, in rats, dexamethasone or adrenalectomy affects catecholamine biosynthesis in carotid body chemoreceptors and the medullary areas (A2C2, A5, A6, A7) involved in the chemoreflex pathway and the hypoxic ventilatory response (HVR). One dexamethasone injection (1 mg/kg body wt.) stimulated tyrosine hydroxylase activity in the carotid body and had no effect in brainstem catecholamine areas, while HVR was reduced. Chronic dexamethasone (1 mg/kg body wt. daily for 10 days) had a stimulatory influence on tyrosine hydroxylase activity in the carotid body and an inhibitory effect on A2C2, A5 and A7 cell groups. Breathing pattern, but not HVR, was altered. Adrenalectomy elicited an increase in tyrosine hydroxylase activity in A2C2, which was accompanied by a decreased respiratory frequency in hypoxia. The data show that glucocorticoids have differential effects on catecholamine biosynthesis in peripheral and central structures involved in the chemoreflex pathway. Depending on the treatment, the neurochemical changes were accompanied by alterations of HVR or the breathing pattern, which are consistent with a neuromodulating influence of catecholamines on peripheral chemosensory inputs or the central respiratory network.
Adrenalectomy↗
Effects of carotid sinus nerve transection on changes in neuropeptide Y and indolamines induced by long-term hypoxia in rats.
Long-term hypoxia induces changes in neuropeptide-Y-like immunoreactivity (NPY-LI) and/or in the content of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) at the central level. To determine whether these alterations depend on the integrity of carotid body (CB) chemoreceptors, intact rats or those whose carotid sinus nerve was transected (CSNT) were exposed to hypoxia (10% O2) or to normoxia for 14 days. Thereafter, NPY-LI, 5-HT and 5-HIAA levels in discrete brain regions were determined. The increase in NPY-LI in the ventrolateral medulla oblongata (VLM) of intact hypoxic rats was mostly abolished after CSNT and therefore is mainly mediated by CB chemoreceptors. In contrast, other hypoxia-induced changes were similar or even enhanced in CSNT as compared to intact rats and therefore do not depend on the integrity of CB chemoreceptors. This was the case for the increase of NPY-LI in the striatum and the caudal dorsomedian medulla oblongata (DMM), as well as for all the changes in 5-HT and 5-HIAA in the DMM, the VLM, the raphe nuclei, the striatum and the frontal cortex. We propose that long-term hypoxia alters brain NPY-LI and indolamine content through the stimulation of CB chemoreceptors or ancillary chemoreceptors, as well as through local biochemical or morphological mechanisms.
Animals↗
Cooling and asphyxia differentially affect augmented noradrenaline turnover in the brain of the externalized rat foetus.
The object was to investigate the effect of various perinatal conditions particularly cooling and asphyxia on the noradrenaline (NA) turnover in the foetal rat brain. The ratios between the noradrenergic metabolite 3-methoxy-4-hydroxy phenyl-ethylene glycol-sulphate (MHPG) and noradrenaline were determined as indexes of NA-turnover in the cortex and the pons-medulla of the foetal rat brain using high pressure liquid chromatography (HPLC). Rat foetuses were externalized by caesarean section performed on a spinally anaesthesized highly pregnant rat mother. One uterine horn was used as control while the other was exposed to externalization, simulated uterine contractions, cooling or asphyxia. Externalization per se and simulated uterine contractions did not cause any significant change in the NA-turnover. Cooling at 25 degrees C for 20 min caused a significant increase in NA-turnover in the cortex while a significant decrease was observed after 10 min of asphyxia in both the cortex and the pons-medulla and after 15 min in the cortex. We conclude that externalization and simulated uterine contractions per se do not seem to affect the augmented NA-turnover at birth. Cooling caused an increase suggesting a potentiating role on NA-turnover in conjunction with the externalization. On the other hand NA-turnover was depressed by asphyxia, suggesting that the level of oxygen is important for NA neuron activity.
Animals↗
Activity of tryptophan hydroxylase and content of indolamines in discrete brain regions after a long-term hypoxic exposure in the rat.
The influence of long-term hypoxia (10% O2, 14 days) on in vivo activity of tryptophan hydroxylase and on 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentration in discrete brain regions of rats was assessed. The activity of tryptophan hydroxylase was determined through 5-hydroxytryptophan accumulation (5-HTPacc) following the administration of NSD 1015. The 5-HTPacc was significantly decreased in the dorsal and median raphe (56 and 42%, respectively) and in the striatum (62%). Both 5-HTPacc and the ratio of the concentrations of 5-HIAA to 5-HT were decreased in the nucleus raphe magnus (46 and 27%, respectively), the dorsomedian medulla oblongata (52 and 51%), the locus coeruleus (62 and 40%) and the anterior hypothalamic nucleus (30 and 50%). In contrast, 5-HTPacc was increased in the ventrolateral medulla oblongata (55%) and the preoptic area (83%), but the 5-HIAA/5-HT ratio was lower in these two regions. Finally, 5-HIAA/5-HT ratio was also decreased in the periventricular nucleus and in the frontal cortex. Since various patterns of variations in 5-HTPacc and in 5-HIAA/5-HT ratio were observed, the factors affecting serotonin metabolism in hypoxic rats can be different among brain regions. These results show that, in the rat, long-term hypoxia induces changes in in vivo activity of tryptophan hydroxylase and in 5-HT and 5-HIAA content of some brain structures; some of these biochemical changes may be linked to adaptative mechanisms.
5-Hydroxytryptophan↗
Long-term influence of neonatal hypoxia on catecholamine activity in carotid bodies and brainstem cell groups of the rat.
1. In order to determine the long-term influence of neonatal hypoxia on catecholaminergic activity in peripheral arterial chemoreceptors and brainstem noradrenergic cell groups (A1, A2, A5 and A6), 1-day-old male rat pups were subjected to hypoxia (10% oxygen) for 6 days and then supplied with normal air. Control animals were kept at normoxia from birth. Rats were killed at either 3 or 8 weeks of age. 2. The content of dopamine and noradrenaline in carotid bodies of neonatally hypoxic rats was increased at both 3 and 8 weeks of age. 3. Noradrenaline turnover was selectively decreased in the caudal portion of A2 (located in the area of chemosensory afferent projection) at 8 weeks of age (-76 +/- 2%), while this turnover was unaffected in rostral A2 cells. Noradrenergic activity in A1, A5 and A6 was altered by neonatal hypoxia in an age-dependent fashion. 4. The data suggest that neonatal hypoxia induces long-term changes in the basal activity of the carotid body and brainstem noradrenergic cell groups. Such changes might contribute to neuronal regulation of the delayed respiratory, arousal and neural sequelae associated with neonatal hypoxia. These changes could also be involved in the early programming of respiratory and blood pressure control.
Animals↗
Neonatal hypoxia disturbs the catecholamine turnover in the nucleus of the tractus solitarius and the peripheral chemoreceptors of the adult rat.
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Animals↗
Effects of hydration state on hormonal and renal responses during moderate exercise in the heat.
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 degrees 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 (osm[pl]), 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 osm(pl) 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.
Adrenal Glands↗
Influence of gender and endogenous sex steroids on catecholaminergic structures involved in physiological adaptation to hypoxia.
Mechanisms underlying sex-related differences in adaptation to high altitude were investigated by assessing the turnover of dopamine and noradrenaline in structures of the chemoafferent pathway, i.e. carotid body and brainstem noradrenergic cell groups (A1, A5, A6, A2 to which chemosensory fibres project). The influence of gender was assessed in male and female rats reared at an altitude of 3600 m, whereas the influence of endogenous sex hormones was evaluated by castration. Haematocrit, red blood cell count and plasma erythropoietin levels were lower in females than in males (-5%, -15%, -53%, respectively). Dopamine and noradrenaline turnover were higher in female structures (carotid body: +51%; A2: +140%; A1: +54%; A5: +27%). Dopamine and noradrenaline turnover in carotid body and brainstem cell groups were differently affected by castration, i. e. enhanced by orchidectomy (carotid body: +134%; A2: +120%; A1: +69%; A5: +67%) but inhibited by ovariectomy (carotid body: -33%; A2: -92%). Orchidectomy elicited a reduction in haematocrit (-10%), haemoglobin concentration (-8%) and red blood cell count (-24%), whereas haematological status remained unaltered after ovariectomy. Therefore, both gender and endogenous sex steroids may control catecholamine activity differently in structures involved in the chemoafferent pathway, thus providing a neurochemical basis for sex-related differences in adaptation to hypoxia.
Adaptation, Physiological↗
Long-term exposure to ozone alters peripheral and central catecholamine activity in rats.
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.
Adrenal Glands↗