Doutorado em Ciências Fisiológicas

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Navegando Doutorado em Ciências Fisiológicas por Autor "Amaral, Sandra Lia do"

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    Baixa concentração de ouabaína promove aumento da liberação de óxido nítrico mediada pela AKt, em anéis de aorta de ratos com e sem sinais de insuficiência cardíaca após infarto do miocárdio
    (Universidade Federal do Espírito Santo, 2011-03-31) Siman, Fabiana Dayse Magalhães; Vassalo, Dalton Valentim; Padilha, Alessandra Simao; Endringer, Denise Coutinho; Stefanon, Ivanita; Rossoni, Luciana Venturini; Amaral, Sandra Lia do
    Ouabain (OUA) is an endogenous compound present in nanomolar concentration in the plasma of mammals. In myocardial infarction (MI) and in heart failure (HF) plasma OUA concentration is increased. Previous reports have demonstrated that OUA may have a primary role in causing cardiac dysfunction and failure, may act as marker that predicts the progression of HF. However, the vascular effects of OUA in the MI and in the HF have not been reported yet. Thus, the present study investigated the acute effects of 3nM of OUA on the vascular reactivity of rats that developed or not HF after MI, and proposed the possible mechanisms of action of digitalis. For this, the MI was induced by coronary ligation and the animals were divided in three groups: fictitious surgery (SHAM), INF (rats without signs of HF) and IC (rats with signs of HF). Four weeks after MI, were evaluated the weight and hemodynamic parameters of the three groups, and vascular reactivity to phenylephrine (PHE) in aortic rings in the presence and absence of the OUA. The IC group showed decreased body weight (BW), increased lung/BW ratio and right ventricle/BW ratio, compared to other groups. The INF group showed increased lung/BW ratio and right ventricle/BW ratio, compared to SHAM. Infarct size was similar in both groups. Regarding hemodynamic parameters, we observed an increase in left ventricular end diastolic pressure (LVEDP) in group IC compared to the others. Moreover, we observed a reduction of the positive and negative rates of pressure development in the INF and IC. The response to PHE increased in IC group and remains unchanged in the INF. The endothelium modulation was smaller in INF compared to SHAM. After incubation with OUA, we observed a reduction in response to PHE in all groups. This effect was mediated by endothelium. The incubation with L-NAME increased the reactivity to PHE in all groups, but, this response was smaller in INF and IC groups. The incubation with L-NAME+OUA potentiated the response to PHE in the three groups, suggesting that OUA increases nitric oxide (NO) production. Aminoguanidine did not alter the reactivity to PHE in the three groups, but, after incubation with aminoguanidine+OUA, the response to PHE in INF and IC increased. This suggests the participation of NO derivate of iNOS in the OUA effects. The wortmannin did not alter the response to PHE in the three groups. However, the incubation with wortmannin+OUA increased the response to PHE in INF and IC groups. This suggests the participation of PI3K/Akt patways in the NO production induced by OUA. The TEA increased the reactivity to PHE in all groups, but this effect was smaller in INF group. The coincubation with TEA and OUA increased this response in INF and IC groups, suggesting that OUA stimulates the release of a factor that seems to open potassium channels. The protein expression of eNOS, Akt and pAkt was not different between groups. However, in the presence of OUA, we observed an increased of pAkt/Akt ratio in the INF and IC groups. Results presented in the current study suggest that OUA decreases vascular reactivity to PHE in SHAM, INF and IC. This reduction in response to PHE is associated with an increased bioavailability of NO. Therefore, the OUA is able to increase NO production, but acts through different mechanisms. In the SHAM rats, OUA increases NO production by independent mechanism of iNOS and PI3K/Akt patways. In the INF and IC rats, the OUA increases NO production by dependent mechanism of iNOS and PI3K/Akt patways. Moreover, in these latter groups, the OUA also increases potassium channels activation. These results suggest a beneficial effect of the OUA after MI and HF, since that this digitalis is capable of reversing, at least partially, the reduction of vasodilators factors, such as NO and a factor that seems to open potassium channels, in those conditions.