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It has been proposed that histamine is an excitatory transmitter between the glomus cells of the carotid body (CB) and the nerve endings of the petrosal ganglion (PG) neurons. The histamine biosynthetic pathway and the presence of histamine H1, H2 and H3 receptors have been reported in the CB. Thus, histamine meets some of the criteria to be regarded as a transmitter. However, there is no evidence...
Experiments using live dissociated carotid body (CB) cells for patch clamping, [Ca++]i or other measurements require positive identification of the cell being recorded. At present, cell morphology is usually employed, but several cell types within the carotid body evidence similar morphologic characteristics. Therefore, we sought to develop a method utilizing a vital dye to identify glomus cells before...
Neuroglobin (Ngb) is a member of the vertebrate globin family expressed particularly in the brain and in the retina. Ngb is concentrated in the mitochondria-containing areas of neurons, and its distribution is correlated with oxygen consumption rates. Previously we have shown that Ngb is expressed in carotid body (CB) tissues. Considering that hypoxia and aging may be linked through a series of adaptive...
For mammals, oxygen sensing is fundamental to survive. An adequate response to reduced oxygen tension, herein termed hypoxia, requires an instantaneous adaptation of the respiratory and the circulatory systems. While the glomus caroticum as well as the pulmonary and systemic vasculature and potentially also the airway chemoreceptors enable a corresponding response within seconds, changes in gene expression...
The carotid body (CB) plays important roles in cardiorespiratory changes in intermittent hypoxia (IH). Erythropoietin (EPO), a hypoxia-inducible factor (HIF)-1 target gene, is present in the chemoreceptive type-I cells in the CB but its expression and role in IH resembling sleep apnoeic conditions are not known. We hypothesized that IH upregulates the expression of EPO and its receptor (EPOr) in the...
Chelation of iron in in vitro carotid body emulates the effects of hypoxia. The role iron plays in in vivo ventilatory responses is unclear. In the current study we addressed this issue by examining the effects of chronic iron chelation on the hypoxic ventilatory response in 9 conscious Wistar rats. Acute responses to 14 and 9% O2in N2 were recorded in the same rat before and then after 7 and 14 days...
The carotid body is stimulated by a number of blood-borne stimuli, ranging from increasing intensities of hypoxia, hypercapnia or acidosis to less studied stimuli, including hyperthermia, hyperosmolarity and hyperkalaemia. Although there exists heterogeneity in type I cell structure and function, there is no evidence to demonstrate that individual afferent fibres of the carotid sinus nerve subserve...
Peripheral arterial chemoreceptors in the carotid body (CB) are modulated by pH/CO2. Soluble adenylyl cyclase (sAC) is directly stimulated by bicarbonate ions (HCO3). Because CO2/HCO3 mediates depolarization in chemoreceptors, we hypothesized that sAC mRNA would be expressed in the CB, and its expression and function would be regulated by CO2/HCO3. Sprague-Dawley rats at postnatal days 16–17...
Peripheral arterial chemoreceptors, particularly the carotid body chemoreceptors, are the primary sites for the detection of hypoxia and reflexly increase ventilatory drive and behavioral arousal during hypoxic or asphyxial events. Newborn infants are at risk for hypoxic and asphyxial events during sleep, yet, the strength of the chemoreceptor responses is low or absent at birth and then progressively...
Aging is characterized by a lower homeostatic capacity and the carotid body (CB) plays an important role during aging. Here, we sought to elucidate whether the aging effects on the oxygen-sensitive mechanisms in CB cells occur through a reduction of the contact surfaces in the synaptic junctions. The hypothesis was that the CB would undergo a “physiological denervation” in old age. Two groups of male...
Dopamine has been widely used in humans in the management of cardiocirculatory shock, and its inhibitory effect on ventilation has received particular attention in clinical situations more prevalent in the elderly. Dopamine has been extensively studied at the carotid body in adult animals but little is known in aged animals. We investigated the ventilatory responses caused by dopamine in 3 and 24...
Although controversial, animal and tissue studies indicate that carotid bodies are sensitive to changes in glucose as well as in oxygen, thereby functioning as metabolic sensors. This study was designed to test the hypothesis that carotid bodies in humans participate in the counter-regulatory response to insulin-induced hypoglycemia. Dopamine and hyperoxia were used to suppress the carotid...
The excessive hyperventilation seen during exercise in chronic heart failure (CHF) contributes to the limited exercise capacity in this condition. The hyperactivation of reflexes originating, independently, from muscle (ergoreflex) and from chemoreceptors (chemoreflex) has been suggested to play an important part in the mediation of the CHF ventilatory abnormalities. In this study we aimed to assess...
Searching for an arterial chemosensory drive exerted upon the cardiovascular system under eucapnic normoxia, we performed experiments on spontaneously ventilated, pentobarbitone-anesthetized cats, in which ventilatory flow through a pneumo-tachograph, instantaneous respiratory frequency, end-tidal pressure of CO2, arterial pressure, and instantaneous heart frequency were simultaneously recorded. Repeated...
In mammals, transient exposure to hyperoxia for a period of weeks during perinatal life leads to impairment of the ventilatory response to acute hypoxia, which may persist long beyond the duration of the hyperoxia exposure. The impairment of the ventilatory response to hypoxia is due to hyperoxia-induced reduction of carotid chemoreceptor sensitivity to hypoxia. We previously demonstrated that hyperoxia...
Physiological responses to hypoxia either continuous (CH) or intermittent (IH) depend on the O2-sensing ability of the peripheral arterial chemoreceptors, especially the carotid bodies, and the ensuing reflexes play important roles in maintaining homeostasis. The purpose of this article is to summarize the effects of CH and IH on carotid body function and the underlying mechanisms. CH increases baseline...
Obstructive sleep apnoea syndrome (OSAS) is a disorder characterized by repetitive episodes of complete (apnoea) or partial (hypopnoea) obstruction of airflow during sleep. The severity of OSAS is defined by the apnoea hypopnoea index (AHI) or number of obstructive episodes. An AHI greater than 30 is considered severe, but it can reach values higher than 100 in some patients. Associated to the OSA...
It has been proposed that chronic intermittent hypoxia (CIH) contributes to generate hypertension in patients with obstructive sleep apnea syndrome and animal models, due to an enhanced sympathetic outflow. A possible contributing mechanism to the CIH-induced hypertension is a potentiation of carotid body (CB) chemosensory responses to hypoxia, but early changes that precede the CIH-induced hypertension...
Obstructive sleep apnoea is characterized by chronic intermittent hypoxia (CIH) due to recurrent apnoea. We have developed a rat model of CIH, which shows evidence of impaired respiratory muscle function. In this study, we wished to characterize the ventilatory effects of CIH in conscious male and female animals. Adult male (n=14) and female (n=8) Wistar rats were used. Animals were placed in chambers...
In the present study we examined the effects of intermittent (IH) and sustained hypoxia (SH) on low PO2-evoked catecholamine (CA) secretion from neonatal rat chromaffin cells. Experiments were performed on chromaffin cells isolated from rat pups exposed to either IH (P0–P5; 15 s hypoxia-5 min normoxia;8 h/day) or SH (hypobaric hypoxia; 0.4ATM). CA secretion from chromaffin cells was monitored by...
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