RESUMO
We have previously shown that ovariectomy in adult Wistar rats under normal sodium (NS) intake results in an overexpression of the total Na(+)-K(+)-ATPase (NKA) α1-subunit (Di Ciano LA, Azurmendi PJ, Toledo JE, Oddo EM, Zotta E, Ochoa F, Arrizurieta EE, Ibarra FR. Clin Exp Hypertens 35: 475-483, 2013). Upon high sodium (HS) intake, ovariectomized (oVx) rats developed defective NKA phosphorylation, a decrease in sodium excretion, and an increment in mean blood pressure (MBP). Since NKA phosphorylation is modulated by dopamine (DA), the aim of this study was to compare the intracellular response of the renal DA system leading to NKA phosphorylation upon sodium challenge in intact female (IF) and oVx rats. In IF rats, HS caused an increase in urinary DA and sodium, in NKA phosphorylation state, in cytochrome P-4504A (CYP4A) expression, and in 20-HETE production, while MBP kept normal. Blockade of the D1 receptor (D1R) with the D1-like receptor antagonist SCH 23390 in IFHS rats shifted NKA into a more dephosphorylated state, decreased sodium excretion by 50%, and increased MBP. In oVxNS rats, D1R expression was reduced and D3R expression was increased, and under HS intake sodium excretion was lower and MBP higher than in IFHS rats (both P < 0.05), NKA was more dephosphorylated than in IFHS, and CYP4A expression or 20-HETE production did not change. Blockade of D1R in oVxHS rats changed neither NKA phosphorylation state nor sodium excretion or MBP. D2R and PKCα expression did not vary among groups. The alteration of the renal DA system produced by ovariectomy could account for the defective NKA phosphorylation, the inefficient excretion of sodium load, and the development of salt-sensitive hypertension.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/metabolismo , Dopamina/metabolismo , Sódio na Dieta/farmacologia , Envelhecimento , Animais , Modelos Animais de Doenças , Hipertensão/fisiopatologia , Ovariectomia/métodos , Ratos Wistar , Receptores de Dopamina D1/metabolismo , Cloreto de Sódio na Dieta/farmacologia , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
Duration discrimination within the seconds-to-minutes range, known as interval timing, involves the interaction of cortico-striatal circuits via dopaminergic-glutamatergic pathways. Besides interval timing, most (if not all) organisms exhibit circadian rhythms in physiological, metabolic and behavioral functions with periods close to 24â h. We have previously reported that both circadian disruption and desynchronization impaired interval timing in mice. In this work we studied the involvement of dopamine (DA) signaling in the interaction between circadian and interval timing. We report that daily injections of levodopa improved timing performance in the peak-interval procedure in C57BL/6 mice with circadian disruptions, suggesting that a daily increase of DA is necessary for an accurate performance in the timing task. Moreover, striatal DA levels measured by reverse-phase high-pressure liquid chromatography indicated a daily rhythm under light/dark conditions. This daily variation was affected by inducing circadian disruption under constant light (LL). We also demonstrated a daily oscillation in tyrosine hydroxylase levels, DA turnover (3,4-dihydroxyphenylacetic acid/DA levels), and both mRNA and protein levels of the circadian component Period2 (Per2) in the striatum and substantia nigra, two brain areas relevant for interval timing. None of these oscillations persisted under LL conditions. We suggest that the lack of DA rhythmicity in the striatum under LL - probably regulated by Per2 - could be responsible for impaired performance in the timing task. Our findings add further support to the notion that circadian and interval timing share some common processes, interacting at the level of the dopaminergic system.
Assuntos
Ritmo Circadiano/fisiologia , Corpo Estriado/fisiologia , Dopamina/metabolismo , Proteínas Circadianas Period/metabolismo , Substância Negra/fisiologia , Percepção do Tempo/fisiologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Ritmo Circadiano/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Discriminação Psicológica/efeitos dos fármacos , Discriminação Psicológica/fisiologia , Dopaminérgicos/farmacologia , Levodopa/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Estimulação Luminosa , RNA Mensageiro/metabolismo , Distribuição Aleatória , Transdução de Sinais , Substância Negra/efeitos dos fármacos , Percepção do Tempo/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Diuretic and natriuretic effects of renal dopamine (DA) are well established. However, in volume expansion the pattern of renal DA release into urine (UDAV) and the role of enzymes involved in DA synthesis/degradation have not yet been defined. The objective was to determine the pattern of UDAV during volume expansion and to characterize the involvement of monoamine-oxidase (MAO) and aromatic amino-acid decarboxylase (AADC) in this response. In this study male Wistar rats were expanded with NaCl 0.9% at a rate of 5% BWt per hour. At the beginning of expansion three groups received a single drug injection as follows: C (vehicle, Control), IMAO (MAO inhibitor Pargyline, 20 mg/kg BWt, i.v.) and BNZ (AADC inhibitor Benserazide, 25 mg/kg BWt, i.v.). Results revealed that in C rats UDAV (ng/30 min/100g BWt) increased in the first 30 min expansion from 11.5 +/- 1.20 to 21.8 +/- 3.10 (p < 0.05) and decreased thereafter. IMAO showed a similar pattern but significantly higher than C at 30 min expansion (32.5 +/- 2.20, p < 0.05). IMAO greatly reduced MAO activity from 8.29 +/- 0.35 to 1.1 +/- 0.03 nmol/mg tissue/hour and significantly increased diuresis and natriuresis over controls. BNZ abolished the early UDAV peak to 3.2+/-0.72 (p < 0.01) and though, UDAV increased over C after 60 min expansion, natriuresis and diuresis were diminished by BNZ treatment. Results indicate that an increment in renal DA release into urine occurs early in expansion and in a peak-shaped way. In this response MAO plays a predominant role.
Assuntos
Diurese/fisiologia , Dopamina/fisiologia , Rim/fisiologia , Monoaminoxidase/fisiologia , Animais , Descarboxilases de Aminoácido-L-Aromático/fisiologia , Benserazida/farmacologia , Modelos Animais de Doenças , Dopamina/urina , Dopaminérgicos/farmacologia , Masculino , Monoaminoxidase/metabolismo , Natriurese/efeitos dos fármacos , Natriurese/fisiologia , Substitutos do Plasma/administração & dosagem , Pressão Propulsora Pulmonar , Ratos , Ratos Wistar , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/fisiologiaRESUMO
This short memoir conveys a special relationship between a nurse and her patient, a 13-year-old girl who had a liver transplant.
Assuntos
Transplante de Fígado/enfermagem , Relações Enfermeiro-Paciente , Adolescente , Feminino , HumanosRESUMO
The aim of this work was to determine the effect of chronic treatment with 5 mg/kg of tianeptine in male adult Wistar rats separated from the mother as neonates and submitted to variable chronic stress, plasma catecholamines, and anxiety. The plus maze test was performed in order to calculate the anxiety index and catecholamine levels were determined by high-pressure liquid chromatography. Both stress and maternal separation elevated catecholamine levels without affecting anxiety. In the maternally separated stress group, tianeptine decreased epinephrine. Anxiety was reduced in the maternally separated unstressed tianeptine group. Also, all groups showed a tendency to lower anxiety index.
Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Ansiedade de Separação/sangue , Ansiedade de Separação/complicações , Ansiedade/sangue , Ansiedade/tratamento farmacológico , Catecolaminas/sangue , Privação Materna , Estresse Psicológico/sangue , Estresse Psicológico/complicações , Tiazepinas/uso terapêutico , Corticosteroides/sangue , Medula Suprarrenal/fisiologia , Animais , Animais Recém-Nascidos , Ansiedade/psicologia , Ansiedade de Separação/psicologia , Comportamento Animal/fisiologia , Doença Crônica , Feminino , Masculino , Ratos , Ratos Wistar , Estresse Psicológico/psicologiaRESUMO
The present study investigated the effect of early maternal separation on anxiety and hypophyso-adrenal system activity to anterodorsal thalamic nuclei (ADTN) lesion in male rats as adults in order to compare this with previous results with female rats. During the first 3 weeks of life, male rats were isolated 4.5 hr daily and tested as adults. Thirty days after ADTN lesion we found that adrenocorticotropic hormone (ACTH) plasma levels were affected neither by maternal separation nor by ADTN lesion. Plasma corticosterone (CORT) concentration was increased with lesion of the ADTN in maternally separated rats. A significant increase in plasma catecholamine concentration was induced by early maternal separation. In ADTN-lesioned rats, plasma norepinephrine (NE) concentration was significantly lower than in the respective sham-lesioned groups. In terms of anxiety, there were no significant effects of early experience. However, the ADTN lesion tended to decrease anxiety-related behavior.
Assuntos
Glândulas Suprarrenais/fisiologia , Núcleos Anteriores do Tálamo/fisiologia , Ansiedade/psicologia , Privação Materna , Hormônio Adrenocorticotrópico/sangue , Animais , Animais Recém-Nascidos , Comportamento Animal/fisiologia , Epinefrina/sangue , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Bulbo/fisiologia , Norepinefrina/sangue , Ratos , Sistema Nervoso Simpático/fisiologiaRESUMO
The aim of this work was to determine the effect of amitriptyline (AMI) on peripheral outcomes such as plasma epinephrine (E) and norepinephrine (NE) concentration and anxiety-like behavior displayed in the plus maze test in adult male Wistar rats under variable chronic stress and daily oral administration of AMI (5 mg/kg). Animals were previously isolated from the mother for 4.5 hr every day for the first 3 weeks of life. Administration of the antidepressant AMI reduced anxiety-like behavior in animals submitted only to chronic stress but not in early maternally separated (MS) subjects or in animals subjected to the two types of stresses.
Assuntos
Amitriptilina/uso terapêutico , Ansiedade/tratamento farmacológico , Epinefrina/sangue , Norepinefrina/sangue , Estresse Psicológico/tratamento farmacológico , Análise de Variância , Animais , Antidepressivos Tricíclicos/uso terapêutico , Masculino , Privação Materna , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos WistarRESUMO
AIMS: Pheochromocytomas are catecholamine-secreting tumors that also synthesize and secrete several neuropeptides, including opioids. A negative regulation of catecholamine secretion by opioids has been postulated in chromaffin cells. However, results obtained so far are contradictory when referred to human pheochromocytomas. The aim of this study was to define the role of locally produced enkephalins on catecholamine release in human pheochromocytoma cells. MAIN METHODS: Cells obtained from eleven human pheochromocytomas of different genetic origins were cultured for 5 days. Cultures were maintained under basal condition or under enkephalin, dexamethasone and naloxone alone or in combination with enkephalin or dexamethasone-stimulated conditions. Catecholamine and enkephalin levels in the culture medium were measured by HPLC-ED and RIA respectively. KEY FINDINGS: Enkephalin induced a decrease in norepinephrine levels in all tumor cultures. Dexamethasone treatment, which increased enkephalin levels, also decreased catecholamine levels. On the other hand, the addition of naloxone to the cultures reverted to normal the inhibitory action exerted by enkephalin and dexamethasone treatments. SIGNIFICANCE: These results suggest the existence of an autocrine negative regulatory loop exerted by enkephalin on norepinephrine release in human pheochromocytoma cells.
Assuntos
Neoplasias das Glândulas Suprarrenais/metabolismo , Comunicação Autócrina/fisiologia , Catecolaminas/metabolismo , Encefalinas/fisiologia , Feocromocitoma/metabolismo , Adolescente , Adulto , Anti-Inflamatórios/farmacologia , Separação Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Criança , Meios de Cultura , Dexametasona/farmacologia , Encefalina Metionina/metabolismo , Feminino , Humanos , Indicadores e Reagentes , Masculino , Pessoa de Meia-Idade , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologiaRESUMO
To look for a relationship between pineal function in chronic migraine (CM), cluster headache (CH) (during active and remission periods), chronic tension-type headache (CTTH) patients and controls during NREM sleep, REM sleep and waking, we performed serial sampling of plasma melatonin in the different sleep stages during the first half of the night, in order to avoid chronobiological interferences. Plasma melatonin levels did not show a normal curve either in the CTTH or in the CM patients and no significant differences between these groups were found in any of the sleep stages studied. Plasma melatonin values of CH patients during the cluster period showed an abnormal pattern. The curve showed a pathological lack of peaks during the active period, melatonin levels remaining within normal daytime range throughout the study. A trend to normalization of the curve during the remission period was observed. On the basis of these different melatonin secretion patterns, it might be hypothesized that the involvement of the hypothalamus in chronic-type headaches differs from that displayed in episodic forms.
Assuntos
Ritmo Circadiano/fisiologia , Cefaleia Histamínica/sangue , Melatonina/sangue , Transtornos de Enxaqueca/sangue , Fases do Sono/fisiologia , Cefaleia do Tipo Tensional/sangue , Adulto , Idoso , Estudos de Casos e Controles , Doença Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estatísticas não Paramétricas , Vigília/fisiologiaRESUMO
Hypertension in children and adolescents has become a major health problem recently recognized, and in a significant number of patients it is due to an endocrine tumor. The aim of this study was to establish the characteristics of pheochromocytoma in a population of 58 patients between 4 and 20 years of age studied at our Center. They represented a 23% of the total population of 255 pheochromocytoma patients studied. In the younger group (under 20 years of age), there was a marked predominance of severe sustained hypertension (93%), only 7% presented paroxysmal hypertension and none of them was normotensive. The youngsters studied showed a higher incidence of bilateral adrenal pheochromocytoma (34%) and extra-adrenal pheochromocytoma (22%). Malignancy was found in 12% of these patients. In addition, the incidence of familial pheochromocytoma was elevated in these patients (39%). Surprisingly, in contrast with the adult population where the most frequent familial pheochromocytomas were multiple endocrine neoplasia (MEN) type 2A (15%), the younger population showed a higher predominance of von Hippel-Lindau (VHL) (28%) and lower incidence of MEN 2A, MEN 2B, neurofibromatosis (NF), and succinate dehydrogenase subunit B (SDHB). In the VHL group, only two patients belonging to one family, showed the R167W mutation, while the others showed novel mutations in conserved amino acids. It may be speculated that the high incidence of VHL in youngsters may account for the biochemical and clinical features they usually present.
Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Feocromocitoma/patologia , Adolescente , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Feocromocitoma/fisiopatologiaRESUMO
BACKGROUND: It has been demonstrated that the beta-adrenergic signal transduction system is altered somewhere along its pathway in Trypanosoma cruzi infected hearts and we think that these alterations would differ according to the infection phase and the parasite strain. Their study would be important for the understanding of the disease's pathophysiology. METHODS: In the present work we studied important components of this system in mice hearts infected with T. cruzi, Tulahuen strain and with SGO-Z12 isolate, obtained from a patient of an endemic area, in the acute phase of the infection, determining: the plasma catecholamines levels, the beta-receptors density and affinity as well as their function, the cardiac concentration of cAMP and the cardiac contractility as the physiologic response to the initial stimulus. RESULTS: Plasma catecholamines levels were diminished in both infected groups when compared to the uninfected one (P < 0.01). The receptor's affinity was also diminished (P < 0.05) while their density was augmented only in the SGO-Z12 infected one (P < 0.01). The cAMP levels were higher in both infected groups (P < 0.01), the basal contractile force however increased only in the Tulahuen infected one (P < 0.01) while the response to catecholamines remained unchanged. The hearts infected with the SGO Z12 isolate presented an inferior response to epinephrine (P < 0.05) than the ventricles infected with the Tulahuen strain. CONCLUSIONS: This model represents an important approach to understand the biochemical, physiological and molecular changes in the cardiac beta-adrenergic signalling that clearly begin in the acute phase of Chagas' disease and reveal a clear differentiation in the alterations produced by different parasite strains.
Assuntos
Catecolaminas/sangue , Cardiomiopatia Chagásica/sangue , Epinefrina/sangue , Norepinefrina/sangue , Receptores Adrenérgicos beta/análise , Animais , AMP Cíclico/análise , Coração/fisiopatologia , Humanos , Camundongos , Miocárdio/química , Receptores Adrenérgicos beta/fisiologiaRESUMO
We report a novel germ-line point mutation in the von Hippel-Lindau (vhl) gene in a family with childhood occurrence of isolated pheochromocytoma. Two members of this family (the father and his son) were affected. The son had bilateral adrenal pheochromocytoma and the father had one adrenal and one extra-adrenal localization. Both patients presented cardiac arrest while exposed to surgical stress and severe hypoglycemia was registered in the son. The outcome was uneventful. A DNA sequence analysis of vhl tumor suppressor gene revealed the L163R mutation. This new mutation may be specifically associated with the von Hippel-Lindau type 2C disease phenotype. Whether this mutation is linked to the metabolic alterations developed by these patients remains to be determined.
Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Mutação em Linhagem Germinativa , Feocromocitoma/genética , Mutação Puntual , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/genética , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/urina , Adulto , Arginina , Criança , Seguimentos , Genes Supressores de Tumor , Predisposição Genética para Doença , Humanos , Leucina , Imageamento por Ressonância Magnética , Masculino , Linhagem , Feocromocitoma/diagnóstico , Feocromocitoma/urina , Proto-Oncogenes/genética , Análise de Sequência de DNA , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/urinaRESUMO
We evaluated sympathetic nervous system activity by sympathetic skin response (SSR) recording and we further investigated sympathetic and opioid outflow indirectly in patients with features of reflex sympathetic dystrophy by measuring concentrations of plasma catecholamines (CAs) and their metabolites and plasma metenkephalin (ME), before and after corticoid treatment. Six patients were studied. Basal SSR latencies, morphologies and amplitudes were normal in five patients. In one woman, latency and amplitude were also normal but the morphology was disturbed. Basal plasma ME, CA and metabolite levels were similar in the affected and non-affected limbs and a significant increase in plasma ME concentrations was observed in both affected and non-affected limbs after two weeks of steroid treatment. Altogether these results point to an adaptive supersensitivity rather than a sympathetic hyperactivity in this syndrome; also, they indicate that the therapeutic effect of steroids adds, to their known anti-inflammatory action, a stimulatory action on the endogenous opioid system.
Assuntos
Distrofia Simpática Reflexa/diagnóstico , Sistema Nervoso Simpático/fisiologia , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Catecolaminas/sangue , Encefalinas/sangue , Feminino , Resposta Galvânica da Pele/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Distrofia Simpática Reflexa/sangue , Distrofia Simpática Reflexa/tratamento farmacológicoRESUMO
OBJECTIVE: The objective of this study is to present the clinical findings and outcome of a large cohort of pregnant women with pheochromocytoma (PHEO) with the aim to contribute to the better recognition, detection and management of pregnancy-related PHEO in the population of pregnant patients with hypertension. METHODS: This is a longitudinal follow-up of a single cohort of 15 patients aged 19-40 years with PHEO associated with pregnancy. Urinary catecholamines and vanillylmandelic acid (VMA) were analysed. Ret proto-oncogene, SDHB and VHL mutations were determined in germline DNA from seven women using PCR followed by direct sequencing. RESULTS: During pregnancy, all women presented typical features of catecholamines excess. Nevertheless, biochemical diagnosis was performed only in four out of 15 cases during pregnancy and postpartum in the remaining 11. Paroxysmal hypertension was the predominant pattern. Urinary catecholamines and/or VMA were increased in all patients. Tumours were adrenal in 13 patients and extraadrenal in two. Mutations in the Ret proto-oncogene were found in four patients, in the VHL gene in one and in the SDHB gene in one. Antihypertensive treatment resulted in effective control of blood pressure and all women survived. In the group of women diagnosed postpartum, one foetus demised. Newborns from mothers receiving adequate treatment survived. One woman left the hospital after caesarean section but before PHEO surgery became pregnant again and this gestation ended with maternal-foetal dead. CONCLUSION: A high index of suspicion in all pregnant women presenting hypertension mainly paroxystic during any gestational phase and/or a history of familial PHEO are the keys to disclose this important diagnosis.
Assuntos
Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Hipertensão/complicações , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Neoplasias das Glândulas Suprarrenais/genética , Adulto , Estudos de Coortes , Feminino , Humanos , Hipertensão/genética , Recém-Nascido , Estudos Longitudinais , Mutação , Feocromocitoma/genética , Gravidez , Complicações Cardiovasculares na Gravidez/genética , Complicações Neoplásicas na Gravidez/genética , Resultado da Gravidez , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-ret/genética , Succinato Desidrogenase/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Adulto JovemRESUMO
The chronic indeterminate form of Trypanosoma cruzi infection could be the key to knowing which patients will develop chagasic myocardiopathy. Infected mice present a period in which cardiac functional and structural alterations are different from those described for acute or chronic phases. We studied some components of the cardiac ß-adrenergic system in mouse hearts infected with T. cruzi Tulahuen strain or SGO-Z12 isolate during the chronic indeterminate phase of infection. We determined: (i) the primary messenger (epinephrine and norepinephrine) levels in plasma by reverse-phase-HPLC; (ii) the cardiac ß-adrenergic receptors' (ß-AR) density and affinity by binding with tritiated dihidroalprenolol and by immunofluorescence; (iii) the cardiac concentration of the second messenger (cAMP) (by ELISA) given its importance for the phosphorylation of the proteins involved in cardiac contraction; (iv) the cardiac contractility and functional studies of the ß-ARs as a response to the ligand binding to the receptor; and (v) the left ventricular ejection fraction as a measure of in vivo cardiac function. Plasma catecholamines levels remained similar to those found in uninfected controls. The ß-ARs' affinity decreased in both infected groups compared with the uninfected group (P<0.05) while the receptors' density increased only in the SGO-Z12 group (P<0.01). Cyclic AMP levels were higher in both infected groups (P<0.01) relative to controls, and were higher in SGO-Z12-infected mice compared with those infected with the Tulahuen strain. However, the basal contractile force remained unchanged and the response to catecholamines only increased in the Tulahuen group (P<0.05). The left ventricular ejection fraction, on the other hand, was diminished in SGO-Z12-infected mice. Heterogeneity between T. cruzi strains determine, in the chronic indeterminate form, alterations in the signaling pathways of the ß-adrenergic system at different levels: (i) between catecholamines and the ß(1)-receptors; (ii) between the receptors' activation and the adenylyl-cyclase activation; and/or (iii) between cAMP and the contractile response.
Assuntos
Cardiomiopatia Chagásica/metabolismo , Receptores Adrenérgicos beta/metabolismo , Trypanosoma cruzi/fisiologia , Animais , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/fisiopatologia , AMP Cíclico/metabolismo , Eletrocardiografia , Epinefrina/metabolismo , Coração/parasitologia , Coração/fisiopatologia , Humanos , Camundongos , Contração Miocárdica , Miocárdio/metabolismo , Norepinefrina/metabolismo , Transdução de SinaisRESUMO
Diuretic and natriuretic effects of renal dopamine (DA) are well established. However, in volume expansion the pattern of renal DA release into urine (U DA V) and the role of enzymes involved in DA synthesis/degradation have not yet been defined. The objective was to determine the pattern of U DA V during volume expansion and to characterize the involvement of monoamine-oxidase (MAO) and aromatic amino-acid decarboxylase (AADC) in this response. In this study male Wistar rats were expanded with NaCl 0.9% at a rate of 5% BWt per hour. At the beginning of expansion three groups received a single drug injection as follows: C (vehicle, Control), IMAO (MAO inhibitor Pargyline, 20 mg/kg BWt, i.v.) and BNZ (AADC inhibitor Benserazide, 25 mg/kg BWt, i.v.). Results revealed that in C rats U DA V (ng/30 min/100g BWt) increased in the first 30 min expansion from 11.5 ± 1.20 to 21.8 ± 3.10 (p < 0.05) and decreased thereafter. IMAO showed a similar pattern but significantly higher than C at 30 min expansion (32.5 ± 2.20, p < 0.05). IMAO greatly reduced MAO activity from 8.29 ± 0.35 to 1.1 ± 0.03 nmol/mg tissue/hour and significantly increased diuresis and natriuresis over controls. BNZ abolished the early U DA V peak to 3.2±0.72 (p < 0.01) and though, U DA V increased over C after 60 min expansion, natriuresis and diuresis were diminished by BNZ treatment. Results indicate that an increment in renal DA release into urine occurs early in expansion and in a peak-shaped way. In this response MAO plays a predominant role.
La dopamina (DA) intrarrenal ejerce efectos diuréticos y natriuréticos. Sin embargo, en los estado de expansión de volumen aún no está bien definido el patrón de liberación de dopamina renal hacia la orina y si cumplen un rol las enzimas involucradas en la síntesis o degradación de la amina. El objetivo del presente trabajo fue determinar el patrón de excreción urinaria de DA (U DA V) durante la expansión de volumen, caracterizando la participación de las enzimas monoaminooxidasa (MAO) y decarboxilasa de aminoácidos aromáticos (AADC) en esta respuesta. Para ello ratas Wistar macho fueron expandidas de volumen con NaCl 0.9% al 5% del peso corporal por hora durante dos horas y divididas en tres grupos, los que al comienzo de la expansión recibieron: C (vehículo, Control), IMAO (Pargilina, inhibidor de MAO, 20 mg/kg PC, i.v.) y BNZ (Benserazida, inhibidor de AADC, 25 mg/kg PC, i.v.). Se observó que en C la U DA V (ng/30min/100gPC) aumentó durante los primeros 30 minutos de expansión de 11.5 ± 1.20 a 21.8 ± 3.10 (p < 0.05), disminuyendo posteriormente. IMAO mostró un patrón de liberación similar pero significativamente mayor que C a los 30 min de expansión (32.5 ± 2.20, p < 0.05). En este grupo la actividad de MAO disminuyó de 8.29 ± 0.35 a 1.1 ± 0.03 nmol/mg tejido/hora y aumentaron la diuresis y natriuresis por sobre los controles. En BNZ, el pico de U DA V observado a los 30 min de la expansión disminuyó a 3.2 ± 0.72 (p < 0.01), aunque luego de 60 minutos fue mayor que en C. BNZ disminuyó tanto la diuresis como la natriuresis. Podemos concluir que al comienzo de la expansión de volumen se produce un pico de excreción de dopamina renal hacia la orina. La enzima MAO juega un rol fundamental en esta respuesta.
Assuntos
Animais , Masculino , Ratos , Diurese/fisiologia , Dopamina/fisiologia , Rim/fisiologia , Monoaminoxidase/fisiologia , Descarboxilases de Aminoácido-L-Aromático/fisiologia , Benserazida/farmacologia , Modelos Animais de Doenças , Dopaminérgicos/farmacologia , Dopamina/urina , Monoaminoxidase/metabolismo , Natriurese/efeitos dos fármacos , Natriurese/fisiologia , Pressão Propulsora Pulmonar , Substitutos do Plasma/administração & dosagem , Ratos Wistar , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/fisiologiaRESUMO
La dopamina (DA) renal modula la excreción de sodio y agua y la presión arterial por medio de receptores D1 (D1R) y D2 y es degradada por las enzimas monoamino-oxidasa (MAO) y catecol-O-metiltransferasa (COMT). Nuestro propósito es estudiar el patrón de excreción urinaria de DA (UDAV) y la actividad de MAO y COMT durante el consumo de dietas con distinto contenido de sodio.