ABSTRACT
Abstract Background: Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. Objective: To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. Methods: We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. Results: No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32). Discussion: The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. Conclusion: These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats.
Resumo Fundamento: Expansão de volume extracelular (EVEC) promove alterações da atividade simpática e parassimpática no coração e vasos sanguíneos, os quais podem ser moduladas por vias serotoninérgicas. Objetivo: Avaliar o efeito da administração de salina ou agonista serotoninérgico (DOI) nos núcleos paraventriculares hipotalâmico (NPV) sobre respostas cardiovasculares após EVEC. Métodos: Foram obtidos registros da pressão arterial pulsátil, por meio da artéria femoral, para obtenção dos valores da pressão arterial média (PAM), sistólica (PAS), diastólica (PAD), frequência cardíaca (FC) e razão simpático-vagal (LF/HF) de ratos Wistar antes e após receberem microinjeções bilaterais no NPV de salina ou DOI seguida de EVEC. Resultados: Não foram observadas diferenças significativas dos valores das variáveis estudadas nos diferentes tratamentos do grupo controle. Entretanto, quando os animais são tratados com DOI seguida de EVEC ocorre aumento significativo em relação ao grupo controle com EVEC em todas as variáveis estudadas: PAM (114,42±7,85 vs 101,34±9,17), PAS (147,23±14,31 vs 129,39±10,70), PAD (98,01 ±4,91 vs 87,31±8,61), FC (421,02±43,32 vs 356,35±41,99) e LF/HF (2,32±0,80 vs 0,27±0,32). Discussão: O presente estudo mostrou que a indução de EVEC isotônica não promoveu alterações na PAM, PAD, PAS, FC e LF/HF. Por outro lado, os animais que receberam microinjeção de DOI no NPV seguida de EVEC apresentaram aumento significativo de todas as variáveis. Conclusão: Esses resultados sugerem que a serotonina exerce uma neuromodulação em nivel do NPV, e essa promove uma inibição da resposta barorreflexa frente à EVEC. Assim, o presente trabalho sugere o envolvimento serotoninérgico na neuromodulação no nivel do NPV na resposta reflexa vagal em ratos normotensos.
Subject(s)
Animals , Male , Paraventricular Hypothalamic Nucleus/drug effects , Paraventricular Hypothalamic Nucleus/physiology , Blood Volume/drug effects , Sodium Chloride/pharmacology , Cardiovascular System/drug effects , Serotonin Receptor Agonists/pharmacology , Reference Values , Time Factors , Blood Pressure/drug effects , Blood Pressure/physiology , Blood Volume/physiology , Cardiovascular Physiological Phenomena , Reproducibility of Results , Rats, Wistar , Baroreflex/drug effects , Baroreflex/physiology , Heart Rate/drug effects , Heart Rate/physiologyABSTRACT
Binge alcohol drinking during adolescence has been associated with neurotoxicity and increased risk for the development of alcohol use disorders. There is evidence that acute and chronic ethanol administration alters c-fos expression, an indirect index of cellular activity, in different brain regions in adult rats. We evaluate here if a binge-like pattern of ethanol exposure during adolescence has a relevant impact on basal and/or ethanol-stimulated regional c-fos activity during adulthood. For that aim, Sprague-Dawley rats PND 25 were saline pre-treated, (SP group) or binge-ethanol pre-treated (BEP group) for twoconsecutive days, at 48-h intervals, over a 14-day period (PND 25 to PND 38). At adult stage (PND 63) and following 25 ethanol-free days, we evaluated c-fos immunoreactivity in response to saline or acute ethanol (1.5 or 3.0 g/kg) in the hypothalamus and amygdala. We found that acute ethanol administration dose-dependently increased c-fos activity in the the Paraventricular nucleus of the hypothalamus (PVN). Interestingly, binge-ethanol exposure during adolescence significantly reduced basal c-fos activity during adulthood in the Central nucleus of the amygdala (CeA) and the Arcuate nucleus of hypothalamus (Arc). We conclude that binge-like ethanol administration during adolescence causes long-term disturbances in basal neural activity in brain areas critically involved with ethanol consumption.
El consumo en atracón durante la adolescencia está asociado con neurotoxicidad y con el riesgo de desarrollar un trastorno en el uso de alcohol. Diversos estudios muestran que la administración aguda y crónica de alcohol en ratas adultas altera la expresión de c-fos, un marcador indirecto de actividad celular, en diferentes áreas cerebrales. Nosotros evaluamos si el patrón de consumo de alcohol en atracón durante la adolescencia tiene un impacto en la actividad basal de c-fos en esas regiones activadas por el alcohol. Utilizamos ratas Sprague-Dawley en su día post-natal 25 (PND25) tratadas con suero salino (grupo SP) o con etanol tipo atracón (grupo BEP) durante dos días consecutivos, en intervalos de 48 h, durante 14 días (PND25- PND38). En la edad adulta (PND63) y después de 25 días sin etanol, evaluamos la inmunorreactividad para c-fos en respuesta a una administración aguda de suero salino o etanol (1,5 ó 3,0 g/kg) en diferentes regiones cerebrales. La administración de alcohol incrementó de manera dosis-dependiente la actividad de c-fos en el núcleo paraventricular del hipotálamo. Además la exposición a etanol tipo atracón durante la adolescencia disminuyó la actividad basal de c-fos en la adultez en el núcleo central de la amígdala y en el núcleo arqueado del hipotálamo. Concluimos que el consumo de alcohol en atracón durante la adolescencia causa problemas a largo plazo en la actividad basal de regiones cerebrales implicadas en el consumo de alcohol.
Subject(s)
Animals , Rats , Paraventricular Hypothalamic Nucleus/drug effects , Arcuate Nucleus of Hypothalamus/drug effects , Proto-Oncogene Proteins c-fos/drug effects , Ethanol/administration & dosage , Central Amygdaloid Nucleus/drug effects , Immunohistochemistry , Age Factors , Ethanol/pharmacologyABSTRACT
We determined the effects of DuP753 and PD123319 (both nonpeptides and selective antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar(l), Ala(8)]ANG II (a non-selective peptide antagonist of angiotensin receptors)on water and 3 per cent NaCl intake induced by administration of angiotensin II (ANG II) into the paraventricular nucleus (PVN) of sodium-depleted Holtzman rats weighing 250-300 g. Twenty hours before the experiments, the rats were depleted of sodium using furosemide (10 ng/rat, sc). The volume of drug solution injected was 0.5 mul over a period of 10-15 sec. Water and sodium intake were measured at 0.25, 0.5, 1.0 and 2.0 h. Pre-treatment with DuP753 (l4 rats) at a dose of 60 ng completely abolished the water intake induced by injection of 12 ng of ANG II (15 rats) (6.4 ñ 0.6 vs 1.4 ñ 0.3 ml/2 h), whereas [Sar(l), Ala(8)]ANG II (l2 rats) and PDl23319 (10 rats) at the doses of 60 ng partially blocked water intake (6.4 ñ 0.6 vs 2.9 ñ 0.5 and 2.7 ñ 0.2 ml/2 h, respectively). In the same animals, [Sar(l), Ala(8)]ANG II, DuP753, and PDl23319 blocked the sodium intake induced by ANG II (9.2 ñ 1.6 vs 3.3 ñ 0.6, 1.8 ñ 0.3, and 1.4 ñ 0.2 ml/2 h, respectively). These results indicate that both DuP753 and PD123319, administered into the PVN, blocked the water and sodium intake induced by administration of ANG II into the same site.