Avaliação dos efeitos do peptídeo natriurético atrial sobre a susceptibilidade de crises audiogênica e induzida por pentilenotetrazol

Abstract

The aim of this study was to investigate the effects of atrial natriuretic peptide (ANP) on the susceptibility to audiogenic seizures and those induced by pentylenetetrazole (PTZ). The relationship between ANP and susceptibility to audiogenic seizure was evaluated. Wistar rats and Wistar Audiogenic Rats (WAR) were sacrificed and the concentrations of ANP in plasma and atria were determined by radioimmunoassay. The WAR group was found to have a higher concentration of ANP in plasma and in the atrium. The expression of the gene for ANP was determined by RT-PCR for receptor type A and C in the kidney. There was nodifference between groups for the relative expression of mRNA for the type A receptor. However, the group WAR was found to have a higher relative expression of mRNA the type C receptor. The next step was to determine whether ANP directly favored neuronal excitability in the PTZ model. Wistar rats acutely received 2 L (icv) of saline (0.9%) ordifferent doses of ANP (9.8, 98, 326.5 pmol / animal). The same treatment was repeated in the presence of isatin. After treatment, the animals received PTZ and the seizure threshold was evaluated. No difference was observed between treatments. As the ANP did not favorthe neuronal excitability in the model of seizure induced by PTZ, the relationship between the parameters that control the fluid balance and neuronal excitability in the model of audiogenic seizure was investigated. WAR and Wistar rats were placed in metabolic cages. For 16 daysthe animals received water ad libitum. During this period, WAR rats had higher intake of drinking water excreted higher urine volume with lower osmolality and increased amount of sodium and were found to have a higher glomerular filtration rate. There was no difference in plasma concentrations of sodium, potassium and osmolality and free water clearance. Since there was no difference in the parameters of fluid balance that indirectly influences neuronal excitability, the next hypothesis was to evaluate the effects of ANP on the activity on the hypothalamic -pituitary homeostasis. WAR rats underwent water deprivation for a period of 72 hours. After the sacrifice, the concentrations of ANP were quantified in plasma and atrium, the expression of the gene for ANP in the receptors of type A and C in the kidney and sodium and plasma osmolality. The water deprivation promoted a reduction in plasma ANP and in the atrium. However, all previously differences observed in relation to the parameters of fluid balance were extinguished. In short, there is a relationship between susceptibility to audiogenic seizure and the ANP. However this association is not related to the parameters of fluid balance favoring neuronal excitability. It is a mechanism to compensate the higherintake of drinking water. The activation of the hypothalamic structures involved in fluid balance showed that the model of audiogenic seizure presents a behavioral change. In addition, the ANP has no effect pro or anticonvulsant on PTZ-induced seizures.