RESUMO
The carotid body (CB), a main peripheral arterial chemoreceptor, has lately been implicated in the pathophysiology of various cardiovascular disorders. Emerging experimental evidence supports a causal relationship between CB dysfunction and augmented sympathetic outflow which is the common hallmark of human sympathetic-related diseases, including essential hypertension. To gain insight into the neurotransmitter profile of chemosensory cells in the hypertensive CB, we examined the expression and cellular localization of some classical neurotransmitters, neuropeptides, and gaseous signaling molecules as well as neurotrophic factors and their receptors in the CB of spontaneously hypertensive rats, a common animal model of hypertension. Our immunohistochemical experiments revealed an elevated catecholamine and serotonin content in the hypertensive CB compared to normotensive controls. GABA immunostaining was seen in some peripherally located glomus cells in the CB of SHR and it was significantly lower than in control animals. The density of substance P and vasoactive intestinal peptide-immunoreactive fibers was diminished whereas that of neuropeptide Y-immunostained nerve fibers was increased and that of calcitonin gene-related peptide-containing fibers remained almost unchanged in the hypertensive CB. We have further demonstrated that in the hypertensive state the production of nitric oxide is impaired and that the components of the neurotrophin signaling system display an abnormal enhanced expression. Our results provide immunohistochemical evidence that the altered transmitter phenotype of CB chemoreceptor cells and the elevated production of neurotrophic factors modulate the chemosensory processing in hypertensive animals which contributes to autonomic dysfunction and elicits sympathetic hyperactivity, consequently leading to elevated blood pressure.
Assuntos
Corpo Carotídeo , Hipertensão , Ratos , Animais , Humanos , Ratos Endogâmicos SHR , Pressão Sanguínea , Fatores de Crescimento NeuralRESUMO
The carotid body (CB) is a multipurpose metabolic sensor that acts to initiate cardiorespiratory reflex adjustments to maintain homeostasis of blood-borne chemicals. Emerging evidence suggests that nitric oxide increases the CB chemosensory activity and this enhanced peripheral chemoreflex sensitivity contributes to sympathoexcitation and consequent pathology. The aim of this study was to examine by means of NADPH-diaphorase histochemistry and nitric oxide synthase (NOS) immunohistochemistry the presence and distribution of nitrergic structures in the CB of spontaneously hypertensive rats (SHRs) and to compare their expression patterns to that of age-matched normotensive Wistar rats (NWRs). Histochemistry revealed that the chemosensory glomus cells were NADPH-d-negative but were encircled by fine positive varicosities, which were also dispersed in the stroma around the glomeruli. The NADPH-d-reactive fibers showed the same distributional pattern in the CB of SHRs, however their staining activity was weaker when compared with NWRs. Thin periglomerular, intraglomerular and perivascular varicose fibers, but not glomus or sustentacular cells in the hypertensive CB, constitutively expressed two isoforms of NOS, nNOS and eNOS. In addition, clusters of glomus cells and blood vessels in the CB of SHRs exhibited moderate immunoreactivity for the third known NOS isoenzyme, iNOS. The present study demonstrates that in the hypertensive CB nNOS and eNOS protein expression shows statistically significant down-regulation whereas iNOS expression is up-regulated in the glomic tissue compared to normotensive controls. Our results suggest that impaired NO synthesis could contribute to elevated blood pressure in rats via an increase in chemoexcitation and sympathetic nerve activity in the CB.
Assuntos
Corpo Carotídeo/metabolismo , Hipertensão/metabolismo , NADPH Desidrogenase/metabolismo , Óxido Nítrico/metabolismo , Animais , Imuno-Histoquímica/métodos , Masculino , Óxido Nítrico Sintase/metabolismo , Ratos Endogâmicos SHR , Ratos Wistar , Regulação para CimaRESUMO
The carotid body (CB) is a major peripheral arterial chemoreceptor that initiates respiratory and cardiovascular adjustments to maintain homeostasis. Recent evidence suggests that circulating or locally produced hormones like angiotensin II acting via AT1 receptors modulate its activity in a paracrine-autocrine manner. The aim of this study was to examine the immunohistochemical localization of AT1 receptor in the CB of adult rats and to compare its expression in vehicle-treated animals, and after the long-term application of its selective blocker losartan. Immunohistochemistry revealed that a subset of CB glomeruli and the vast majority of neurons in the adjacent superior cervical ganglion (SCG) were strongly AT1 receptor-immunoreactive. In the CB immunostaining was observed in the chemosensory glomus cells typically aggregated in cell clusters while the nerve fibers in-between and large capillaries around them were immunonegative. Exogenous administration of losartan for a prolonged time significantly reduces the intensity of AT1 receptor immunostaining in the CB glomus cells and SCG neurons. Our results show that AT1 receptors are largely expressed in the rat CB under physiological conditions, and their expression is down-regulated by losartan treatment.
Assuntos
Corpo Carotídeo/química , Receptor Tipo 1 de Angiotensina/química , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Imuno-Histoquímica , Losartan/farmacologia , Masculino , Ratos , Receptor Tipo 1 de Angiotensina/metabolismoRESUMO
INTRODUCTION: Heterotopic gastric mucosa is described almost everywhere in the gastrointestinal tract, from the oral cavity to the rectum. The occurrence of heterotopic gastric tissue in the gallbladder is rare. A choristoma can be defined as a new growth developing from a displaced anlage not normally present in the anatomical site where it developed. We present an extremely uncommon case of a cyst (choristoma) attached to the gallbladder, which contained gastric and intestinal mucosa. CASE PRESENTATION: A 33-year-old woman was hospitalized with clinical symptoms of chronic cholecystitis. The laboratory findings were within the normal range. Abdominal ultrasonography revealed a thickened gallbladder wall and a stone in the cystic duct was suspected. In the course of laparoscopic cholecystectomy, a cyst was visualized in the vicinity of the duct and the gallbladder neck. Microscopic examination of the removed cyst revealed evidence of gastric, duodenal and small-intestinal mucosa. The immunohistochemical study revealed many endocrine cells, which were positive for several endocrine cell markers such as chromogranin, serotonin, gastrin and so on. It can be inferred that the observed cyst had arisen from the foregut early in the development of the gastrointestinal tract. CONCLUSION: The presence of endocrine cells together with epithelial cells supports the hypothesis that these had developed simultaneously, and that the endocrine cells had probably supported the development of the epithelial cells by the release of hormones and growth factors. To the best of the authors' knowledge, this report is the first to report a gastrointestinal cyst choristoma with endocrine cells in the region of the cystic duct and gallbladder.