Browsing by Subject "Carotid body"
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- PublicationOpen AccessCalbindin D-28k immunoreactive nerve fibers in the carotid body of normoxic and chronically hypoxic rats(Murcia : F. Hernández, 2000) Kusakabe, T.; Matsuda, H.; Hirakawa, H.; Hayashida, Y.; Ichikawa, T.; Kawakami, T.; Takenaka, T.The distribution and ultrastructural characteristics of calbindin D-28k immunoreactive nerve fibers were examined in the carotid body of the normoxic control rats by light and electron microscopy, and the abundance of calbindin D-28k fibers in the carotid body was compared in normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). Calbindin D-28k immunoreactivity was recognized in nerve fibers within the carotid body. Calbindin D-28k immunoreactive nerve fibers appeared as thin processes with many varicosities. They were distributed around clusters of glomus cells, and around blood vessels. Immunoelectron microscopy revealed that the calbindin D-28k immunoreactive nerve terminals are in close apposition with the glomus cells, and membrane specialization is visible in some terminals. Some densecored vesicles in the glomus cells were aggregated in this contact region. The chronically hypoxic carotid bodies were found to be enlarged several fold, and a relative abundance of calbindin D-28k fibers was lesser than in the normoxic carotid bodies. When expressed by the density of varicosities per unit area of the parenchyma, the density of calbindin D-28k fibers associated with the glomus cells in chronically hypoxic carotid bodies was decreased by 70%. These immunohistochemical findings indicate a morphological basis for involvement of calcium binding protein in the neural pathway that modulates carotid body chemoreception.
- PublicationOpen AccessChanges in the peptidergic innervation in the carotid body of rats chronically exposed to hypercapnic hypoxia: an effect of arterial CO2 tension(Murcia : F. Hernández, 2002) Kusakabe, T.; Hirakawa, H.; Matsuda, H.; Yamamoto, Y.; Nagai, T.; Kawakami, T.; Takenaka, T.; Hayashida, Y.The abundance of neuropeptide Y (NPY)-, vasoactive intestinal polypeptide (VIP)-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)- immunoreactive nerve fibers in the carotid body was examined in chronically hypercapnic hypoxic rats (10% O2 and 6-7% CO2 for 3 months), and the distribution and abundance of these four peptidergic fibers were compared with those of previously reported hypocapnicand isocapnic hypoxic carotid bodies to evaluate the e ffect of arterial CO2 tension. The vasculature in the carotid body of chronically hypercapnic hypoxic rats was found to be enlarged in comparison with that of normoxic control rats, but the rate of vascular e n l a rgement was smaller than that in the previously reported hypocapnic- and isocapnic hypoxic carotid bodies. In the chronically hypercapnic hypoxic carotid b o d y, the density per unit area of parenchymal NPY fibers was significantly increased, and that of VIP fibers was unchanged, although the density of NPY and VIP fibers in the previously reportetd chronically hypocapnic and isocapnic hypoxic carotid bodies was opposite to that in hypercapnic hypoxia as observed in this study. The density of SP and CGRP fibers was decreased. These results along with previous reports suggest that d i fferent levels of arterial CO2 tension change the p e p t i d e rgic innervation in the carotid body during chronically hypoxic exposure, and altered peptiderg i c innervation of the chronically hypercapnic hypoxic carotid body is one feature of hypoxic adaptation.
- PublicationOpen AccessChronic carotid glomitis in heroin addiction(Murcia : F. Hernández, 2009) Porzionato, A.; Macchi, Verónica; Parenti, Anna; De Caro, RaffaelleThe aim of the present work was to investigate the occurrence and immunological characteristics of chronic carotid glomitis in opiate addicts. Carotid bodies were sampled at autopsy from 50 subjects who died of heroin intoxication (mean age 28 years), and from 16 young (24 years) and 10 older subjects (66 years) who died of trauma. Sections were stained with haematoxylin-eosin and azan-Mallory, and immunohistochemistry was carried out with anti-CD45, -CD3, -CD8, -CD4, -CD20, -CD68, -CD56. Inflammatory aggregates were not observed in young cases, but were found in 21/50 (42%) opiate cases and in 4/10 (40%) older cases. Infiltrates were mainly located in subcapsular and interlobular positions, and were also found around nerve fibres. Inflammatory aggregates were mainly composed of T suppressor/cytotoxic lymphocytes (50-80%). Monocytic/macrophagic cells and B lymphocytes comprised about 10% and 5-20% of inflammatory cells, respectively. T helper lymphocytes were fewer and only rare Natural Killer cells were found. Chronic carotid glomitis must be included among the autopsy findings of opiate addiction, and may be ascribed to inflammatory reactions to exogenous immunogens or to responses to drug-induced degenerative changes of carotid body components.
- PublicationOpen AccessDifferential expressions and roles of hypoxia-inducible factor-1a, -2a and -3a in the rat carotid body during chronic and intermittent hypoxia(Murcia : F. Hernández, 2008) Lam, Siu-Yin; Tipoe, George L.; Liong, Emily C.; Fung, Man-LungThe HIF-1a expression in the carotid body (CB) is central to the transcriptional regulation of the CB structural and functional changes in chronic hypoxia (CH). The CB plays pathogenic roles in cardiovascular morbidity in patients with sleep-disordered breathing; yet, the expression and role of HIF-a subtypes in intermittent hypoxia (IH), resembling recurrent episodic apnea, are unclear. We hypothesized a divergent role of HIF-a subtypes, regulated by differential expression in the CB response to IH. A time-course analysis of the CB volume, and expression profiles of the HIF-1a, -2a, -3a and HIF-regulated gene products, including vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and tyrosine hydroxylase (TH), showed a significant difference in the lack of increase in the rat CB volume, HIF-1a and VEGF expression during IH, despite an increase in the mRNA level of HIF-1a and the prominent increase of volume and expression in the CH group. In contrast, there were increased CB expressions of HIF-2a and -3a, and also ET-1 and TH in both IH and CH groups. Results demonstrated a significant role played by HIF-2a and -3a in the CB response to IH, which could be complementary to the expression and role of HIF-1a under hypoxic conditions. This differential regulation of the HIF-a subtypes and pathways could account for the morphological and neurochemical discrepancy in the CB responses to IH and CH.
- PublicationOpen AccessExpression of inwardly rectifying K+ channels in the carotid body of rat(Murcia : F. Hernández, 2008) Yamamoto, Y.; Ishikawa, R.; Omoe, K.; Taniguchi, K.The inwardly rectifying K+ channels, Kir1.1, Kir2.3, Kir4.1-Kir5.1, and Kir4.2-Kir5.1, are candidate chemosensory molecules for CO2/H+. Here, we determined the mRNA expression and immunohistochemical localization of these channels in the carotid body (CB) and petrosal ganglion (PG) of the rat. RT-PCR analysis revealed mRNA expression of Kir4.1 and Kir5.1 in CB, and Kir1.1, Kir4.1, and Kir5.1 in PG. Immunohistochemistry identified the glomus cells in CB to express both Kir4.1 and Kir5.1 protein, while the nerve fibers in CB were immunoreactive for Kir1.1, Kir4.1, and Kir5.1. In the PG, immunoreactivity for Kir1.1, Kir4.1, and Kir5.1 was observed in some ganglion cells. Our findings suggest that Kir channels in the peripheral chemoreceptors play a role in sensing hypercapnic acidosis and maintaining the resting membrane potentials.
- PublicationOpen AccessHuman carotid body neuroglobin, vascular endothelial growth factor and inducible nitric oxide synthase expression in heroin addiction(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Zara, S.; Porzionato, A.; De Colli, M.; Macchi, V.; Cataldi, A.; De Caro, R.; Di Giulio, C.Aims: The carotid body (CB) represents the prime site for detecting and responding to hypoxia. Since the role of heroin in respiratory depression with consequent hypoxia is known, the authors were able to investigate morphological and molecular modifications occurring in the CB of heroin addicted subjects compared to subjects who died because of trauma. Methods and results: CB sampled from six 27 year old subjects, slides were treated with Mallory Trichrome staining or used for immunohistochemical analysis to detect Neuroglobin (NGB), Hypoxia Inducible Factor-1 (HIF-1α), Vascular Endothelial Growth Factor (VEGF), Inducible Nitric Oxide Synthase (i-NOS), Bax and cleaved Caspase-3 proteins. Mallory Trichrome staining shows an increase in the connective tissue in heroin subjects compared to controls and a parallel reduction in parenchymal area. Immunohistochemical analyses in heroin subjects found a decrease in NGB and an increase in HIF-1α and VEGF compared to controls; i-NOS expression was not statistically significant. Bax and cleaved caspase-3 were positive only in the heroin subjects. Conclusions: These results could confirm the typical hypoxic condition occurring in heroin addicts. Since NGB may function as a reactive oxygen or nitrogen species scavenger and as apoptotic cell death protector, the decrease in its expression may suggest a key role of this globin in human CB impairment due to heroin addiction.
- PublicationOpen AccessMorphological characteristics and peptidergic innervation in the carotid body of spontaneously hypertensive rats(Murcia: F. Hernández, 2011) Takahashi, Masahiro; Matsuda, Hideki; Hayashida, Yoshiaki; Yamamoto, Yoshio; Tsukuda, Mamoru; Kusakabe, TatsumiWe examined morphological characteristics of the carotid body of spontaneously hypertensive rats (SHR), those of age-matched normotensive Wistar rats (NWR), and age-matched genetically comparable Wistar Kyoto rats (WKY). We examined the distribution and abundance of four different regulatory neuropeptides: substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) in the carotid bodies of these three strains of rats. The carotid bodies of SHR were larger than those of NWR and WKY. The values of the long axis of the carotid bodies of SHR were significantly larger (1.3 times) than those of NWR and WKY. In the carotid bodies of SHR, the percentage of relatively large vessels was similar to that of the carotid bodies of WKY, although the carotid bodies themselves were significantly larger than in WKY. The density of VIP varicose fibers in the carotid bodies of SHR was lower than in the carotid bodies of WKY, although the density of SP, CGRP and NPY fibers was similar to that of the carotid bodies of NWR and WKY. These findings suggested that VIP was unrelated to enlargement of the carotid body of SHR, but it might modify the sensitivity of chemoreceptors in the carotid body.
- PublicationOpen AccessSerotonin immunoreacmtivitiyn the carotid body of adult humans(Murcia : F. Hernández, 1994) Habec, J.; Pallot, D.J.; Kummer, W.The distribution of serotonin immunoreactivity (-1R) was studied in adult human carotid bodies, obtained at post-mortem, using both the peroxidaseantiperoxidase method on paraffin sections and a doublelabelling immunofluorescence on frozen sections. Antibodies against synaptophysin and protein gene product (PGP) 9.5 were used for identification of serotonin-1R cells. Serotonin-1R was demonstrable in the carotid bodies of adult humans and it was coexpressed mostly with synaptophysin or PGP 9.5 in type 1 cells. Some serotonin immunopositive type I cells were located in close proximity to capillaries. Serotonin-IR was also observed in a few endothelial cells.
- PublicationOpen AccessSubstance P-like immunoreactivity in rat and cat carotid bodies, Light and electron microscopic studies(Murcia : F. Hernández, 1986) I-li Chen; Yates, Robert D.; Hansen, John T.Substance P-immunoreactive (SP-I) structures in the carotid bodies of rats and cats were examined with the light and electron microscopes. In both species SP-I varicose nerve fibers were located singly in the interstitial connective tissue in close association with blood vessels. They were small unmyelinated fibers enveloped in a common Schwann cell sheath with other SP-negative fibers. Some of SP-I fibers contained large dense-cored granules and small clear vesicles in addition to microtubules and mitochondria and probably represented nerve fiber varicosities. The latter often were found incompletely invested by Schwann cell sheaths. SP-fibers were found occasionally in the envelopes of supporting cells at the periphery of parenchymal cell groups. However, none of the nerve terminals making synaptic contacts with glomus cells exhibited SP-like immunoreactivity. In cat carotid bodies some glomus cells showed moderate to intense SPlike immunoreactivity.The intense SP-I glomus cells displayed numerous dense-cored vesicles of 85 to 140 nm in diameter and frequently showed synaptic contacts with SP-negative nerve terminals. In rat carotid bodies we were unable to detect consistent SP-immunoreactivity in glomus cells. Our results do not favor the hypothesis that SP is a neurotransmitter/modulator in the chemoreceptor afferents synapsing on glomus cells in either the cat or rat carotid body. However our results support the hypothesis that SP in cat glomus cells may play a role in the modulation of chemoreceptor activity.