Influence of long-term hypoxia on tyrosine hydroxylase in the rat carotid body and adrenal gland

Schmitt, Pascal; Garcia, Christine; Soulier, V.; Pujol, J.F.; Péquignot, Jean-Marc

doi:10.1016/0165-1838(92)90221-2

Cited by 24 publications

(11 citation statements)

References 25 publications

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“…14 An intriguing observation is that neither SH or IH altered catecholamine content in SCGs or AGs and that the effects on expression of catecholamine synthesizing enzymes were very small. These results differ somewhat from the earlier reports showing an increase in TH protein in AGs from rats exposed to SH for up to 22 days 46 and in DA but not NE in SCGs. 47 A possible explanation for this discrepancy is that catecholamine contents in these studies were expressed per individual ganglion or gland, the size of which increases with chronic hypoxia, whereas our measurements were normalized to protein content in each tissue.…”

Section: Effects Of Sh and Ih On Content Of Biogenic Amines In Cb Sccontrasting

confidence: 57%

Regulation of Catecholamines by Sustained and Intermittent Hypoxia in Neuroendocrine Cells and Sympathetic Neurons

et al. 2003

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Abstract-Chronic intermittent hypoxia, a characteristic feature of sleep-disordered breathing, induces hypertension through augmented sympathetic nerve activity and requires the presence of functional carotid body arterial chemoreceptors. In contrast, chronic sustained hypoxia does not alter blood pressure. We therefore analyzed the biosynthetic pathways of catecholamines in peripheral nervous system structures involved in the pathogenesis of intermittent hypoxia-induced hypertension, namely, carotid bodies, superior cervical ganglia, and adrenal glands. Rats were exposed to either intermittent hypoxia (90 seconds of room air alternating with 90 seconds of 10% O 2 ) or to sustained hypoxia (10% O 2 ) for 1 to 30 days. Dopamine, norepinephrine, epinephrine, dihydroxyphenylacetic acid, and 5-hydroxytyptamine contents were measured by high-performance liquid chromatography. Expression of tyrosine hydroxylase and its phosphorylated forms, dopamine ␤-hydroxylase, phenylethanolamine N-methyltransferase, and GTP cyclohydrolase-1 were determined by Western blot analyses. Both sustained and intermittent hypoxia significantly increased dopamine and norepinephrine content in carotid bodies but not in sympathetic ganglia or adrenal glands. In carotid bodies, both types of hypoxia augmented total levels of tyrosine hydroxylase protein and its phosphorylation on serines 19, 31, 40, as well as levels of GTP cyclohydrolase-1. However, the effects of intermittent hypoxia on catecholaminergic pathways were significantly smaller and delayed than those induced by sustained hypoxia. Thus, attenuated induction of catecholaminergic phenotype by intermittent hypoxia in carotid body may play a role in development of hypertension associated with sleep-disordered breathing. The effects of both types of hypoxia on expression of catecholaminergic enzymes in superior cervical neurons and adrenal glands were transient and small. Key Words: blood pressure Ⅲ catecholamines Ⅲ chemoreceptors Ⅲ sympathetic nervous system Ⅲ sleep apnea syndromes Ⅲ oxygen Ⅲ adrenal gland S leep-disordered breathing (SDB) is a frequent condition that affects Ϸ5% of the population and is characterized by repetitive episodes of hypoxemia and hypercapnia, followed by arousal, respiratory recovery, and reoxygenation. Persistent SDB is causally associated with substantial cardiovascular morbidity, the most important being systemic arterial hypertension (for recent comprehensive review, see Fletcher, 2003 1 ). The mechanisms involved in the genesis of this hypertension appear to involve several different components including augmented sympathetic nerve activity, 1-4 altered function of arterial chemoreceptors, 1,5-7 elevated levels of circulating norepinephrine (NE), 8 -10 decreased vascular responses to nitric oxide, 11 increased plasma concentrations of endothelin, 12,13 and altered regulation of the renal kallikrein-kallistatin pathway. 14 The use of animal model systems in which different components of SDB can be studied individually have revealed that intermittent hy...

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Section: Effects Of Sh and Ih On Content Of Biogenic Amines In Cb Sccontrasting

confidence: 57%

Regulation of Catecholamines by Sustained and Intermittent Hypoxia in Neuroendocrine Cells and Sympathetic Neurons

et al. 2003

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“…Prolonged hypoxic conditions have been shown to result not only in increased production and secretion of neurohypophysial hormones in experimental animals [71]but also to exert a stimulatory influence on both TH protein and TH mRNA levels [72, 73, 74]. In PC12 pheochromocytoma cell lines, molecular studies indicated that the stability of the TH mRNA triples during hypoxia and is associated with increased TH protein synthesis and increased neurotransmitter dopamine release [75].…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of Tyrosine Hydroxylase Immunoreactivity in Paraventricular and Supraoptic Neurons in Illnesses with Prolonged Osmotic or Nonosmotic Stimulation of Vasopressin Release

Panayotacopoulou¹,

Malidelis²,

Fliers³

et al. 2002

Neuroendocrinology

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Our previous studies indicated that in the human paraventricular (PVN) and supraoptic (SON) nuclei, tyrosine hydroxylase (TH) – the first and rate-limiting enzyme in catecholamine synthesis – is localized mainly in magnocellular neurons and that antemortem factors regulate its expression. The purpose of the present study was to investigate the distribution of TH-immunoreactive (TH-IR) perikarya of the hypothalami of a large sample of well-documented adult subjects without neurological, psychiatric or endocrinological disease in order to identify factors that could regulate the expression of TH in the human neurosecretory neurons. Our material consisted of the hypothalami of 38 subjects studied immunohistochemically for TH using the peroxidase-antiperoxidase method. Striking individual differences were observed among the subjects studied concerning the number and distribution of TH-IR perikarya within the PVN and SON. These differences were evident throughout the entire rostrocaudal length of the hypothalamus and appeared to be related neither to the age or sex of the subjects nor to the postmortem interval or staining procedures. In the sample studied, a large number of TH-IR perikarya were observed specifically in all subjects that had suffered from right-sided heart failure due to pulmonary hypertension, liver cirrhosis or dehydration. In all the above illnesses, increased production and secretion of vasopressin (VP) are reported to occur due to a decrease in ‘effective’ blood volume or to osmotic stimulation. We conclude that somatic illnesses leading to prolonged osmotic or nonosmotic stimulation of VP release may induce increased expression of TH immunoreactivity in the human neurosecretory neurons related to neuronal activation.

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“…Moreover, the content of tyrosine hydroxylase (TH), was gradually increased in rat CBs after adaptation to hypoxia, and the turnover of DA and NE in in vitro CB culture was increased by 15- and 5-fold, respectively [49]. The activity of the plasma enzyme dopamine-β-hydroxylase has been reported to be increased due to exposure to altitude hypoxia [50].…”

Section: Discussionmentioning

confidence: 99%

Geriatric Men at Altitude: Hypoxic Ventilatory Sensitivity and Blood Dopamine Changes

et al. 2000

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Background: Short-term exposure to high-altitude hypoxia increases hypoxic ventilatory sensitivity (HVS) in healthy humans. Dopamine (DA) is the implicated neurotransmitter in carotid body (CB) chemoreceptor response, and the microenvironmental conditions in CB tissue are comparable to blood. Continuous DA infusion affected ventilation in animals and humans. Age-related oscillations in blood DA levels may influence peripheral chemoreflexes. Objective: Hypoxic ventilatory responses (HVR) relative to blood DA concentration and its precursor, dihydroxyphenylalanine (DOPA) was measured in young and elderly men during short-term altitude adaptation. Methods: Nine elderly climbers (group 1: 61 ± 1.4 years) and 7 young healthy subjects (group 2: 23 ± 2 years) were tested at sea level on day 0, on day 3 after passive transport to 2,200 m, and on day 14 after climbing to 4,200 and 5,642 m. Results: Sea level HVR in group 1 was 47% lower than in group 2, accompanied by higher blood DOPA (300%) and DA (37%) content. Initial DA and DOPA concentrations showed a negative correlation with initial HVR but a positive correlation with age. Passive transport to middle altitude (2,200 m) increased HVS, doubling HVR slopes in groups 1 and 2 and producing increased maximum expired minute ventilation during isocapnic rebreathing (29 and 28%, respectively). Day 3 2,200-meter blood DOPA content decreased by 22% in group 1 and increased by 300% in group 2. DA increased in both groups. Conclusion: The relationship between HVR and the reciprocal DA and DOPA values seen in both groups is associated with age, producing decreased DA receptor sensitivity and enhanced DA reuptake during adaptation to high altitude.

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Influence of long-term hypoxia on tyrosine hydroxylase in the rat carotid body and adrenal gland

Cited by 24 publications

References 25 publications

Regulation of Catecholamines by Sustained and Intermittent Hypoxia in Neuroendocrine Cells and Sympathetic Neurons

Regulation of Catecholamines by Sustained and Intermittent Hypoxia in Neuroendocrine Cells and Sympathetic Neurons

Increased Expression of Tyrosine Hydroxylase Immunoreactivity in Paraventricular and Supraoptic Neurons in Illnesses with Prolonged Osmotic or Nonosmotic Stimulation of Vasopressin Release

Geriatric Men at Altitude: Hypoxic Ventilatory Sensitivity and Blood Dopamine Changes

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