Avaliação do Tratamento a Curto Prazo Com Ouabaína na Reatividade Vascular de Rato.

• Autor(a) principal: Padilha, Alessandra Simão
• Data de Publicação: 2007
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
• Texto Completo: http://repositorio.ufes.br/handle/10/5167
• topic: Fisiologia; 612

Ouabain (OUA), an inhibitor of the Na+K+ ATPase (NKA), is an endogenous compound present in namolar concentration in the plasma of several mammalians. In several models of hypertension plasma OUA concentration is increased suggesting an association to the genesis and/or maintenance of hypertension. In this study pressor changes resulting from the acute administration of OUA 18µg/Kg (i.v.) (~30 nmol/Kg) were evaluated in normotensive (Wistar and WKY) and spontaneously hypertensive rats (SHR). At the same time, were evaluated the effects of 1µM OUA in the reactivity of the tail vascular bed to phenylephrine (PHE) in Wistar, WKY and SHR. On the order hand, the vascular reactivity and the role of endothelial factors in mesenteric resistance arteries (MRA) in 15 day chronic oubain treated rats were also investigated. The systolic (SBP) and diastolic (DBP) blood pressure were increased by the acute administration of 18µg/Kg of OUA in Wistar and SHR, but not in WKY. The pretreatment with losartan (10 mg/kg), an inhibitor of AT1 receptors, only blocked the effects of OUA in the DBP in Wistar, without altering the other parameters. In the tail vascular bed, the perfusion with OUA in the presence of endothelium (E+) increased the vascular reactivity of PHE in the all groups. In the absence of functional endothelium, the effects of OUA were abolished. However, in E+, after perfusion with losartan (10-4M) plus OUA, the increase of response to PHE by OUA was totally abolished in Wistar and WKY, and partially in SHR. The chronic ouabain treatment for 15 days increased SBP, DBP and heart rate. However, this treatment did not change the pressor response to PHE. The endothelium removal or the nitric oxide synthase (NOS) inhibitor (L-NAME, 10-5M) increased the responses to α-adrenergic agonists. The endothelial modulation was similar in treated and untreated rats, but the L-NAME effects were more increased in MRA in treated rats. Endothelial NOS expression and relaxation of acetilcholine remained unaltered after ouabain treatment. To evaluated the prostanoids participation in the response to PHE, the MRA were incubated with Indometacin (10-4M), an inhibitor of cyclooxigenase, plus LLNAME. In the same protocol, EDHF participation was investigated, after incubation of MRA with Indometacin and L-NAME plus TEA (2mM), an inhibitor of calcium activated potassium channels. Indometacin plus L-NAME, shifted leftward the concentration-response curves to PHE in MRA from untreated rats and this response was similar when compared the leftward shift after incubation only L-NAME. However, in MRA of the treated rats, the co-incubation with Indometacin plus L-NAME did not altered concentrationresponse curves to PHE. This result was accompanied by increase in the COX-2 expression. TEA shifted the PHE curves further leftward only in MRA from untreated rats. In conclusion, these results suggest that the increase in the DBP in Wistar after 18µg/Kg OUA depends of angiotensin II. In the tail vascular bed of normotensive and hypertensive rats, the acute administration of 1µM OUA, increased of PHE pressor response. The endothelium modulates this response by releasing angiontensin II in normotensive rats, but in hypertensive rats, other factors seem to be involved besides the angiotensina II. The chronic ouabain treatment for 15 days modified the participation of endothelial factors in response to PHE in MRA, by the increase liberation of NO and prostanoids, and impairment of EDHF release. This was accompanied by an increased COX-2 expression. Although this balance avoids changes in the PHE concentration-response curves these vascular changes might contribute to maintain the ouabain-induced hypertension.