Influência do tratamento com doses nanomolares de ouabaína na reatividade vascular em artérias de condutância em ratos

• Ano de defesa: 2009
• Autor(a) principal: Batista, Priscila Rossi de
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Mestrado em Ciências Fisiológicas; Centro de Ciências da Saúde; UFES; Programa de Pós-Graduação em Ciências Fisiológicas
• Palavras-chave em Português: Fisiologia; 612
• Link de acesso: http://repositorio.ufes.br/handle/10/7925

Ouabain is a cardiac glycoside found in the plasma of mammals at nanomolar concentrations, which may be elevated in several models of arterial hypertension, suggesting an association with its genesis or maintenance. However, studies of vascular reactivity in the early stages of arterial hypertension induced by ouabain have not been developed in conductance arteries yet. Therefore, the aim of this study was to evaluate the effect of treatment with ouabain for 15 days in the vascular reactivity of the proximal segment of the caudal artery of rats, which, in turn, behaves as a conductance vessel. We used Wistar rats (n = 68, 250 – 350g), divided into control group and treated with ouabain, in the concentration of 25µg/kg/day, for 15 days. Animals were anesthetized with urethane (1,2g/kg, i.p.) and heparinized. After 10 minutes, hemodynamic measurements in vivo were performed. Then the proximal segment of the caudal artery was cannulated with a catheter filled with nutrient solution. The tail was then sectioned at its proximal third and perfused with Krebs solution under constant flow (2,5ml/min) at 36°C. The perfusion system was connected to a pressure transducer connected to a data acquisition system, connected to a computer for continuous recording of average perfusion pressure. The preparation was subjected to the stabilization of 45 minutes so the experimental protocols were started. Vascular reactivity to phenylephrine (FE) (0,001-100µg, in bolus) was assessed in the presence and absence of endothelium. The involvement of endothelial factors were analyzed by dose-response curves to FE before and after administration of L-NAME (100mM), tetraethylammonium (TEA, 5mM), indomethacin (10mM), and finally co-administration with indomethacin and L-NAME in order to investigate, respectively, nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), prostanoids, and the interaction of NO and prostanoids. The functional activity of Na+K +ATPase was analyzed by the curve of relaxation to KCl. The doseresponse curves to FE were analyzed using the difference of area under the curve (%dAUC). Data are presented as mean ± SEM. Statistical analysis was performed using paired and unpaired t test, and p<0.05 was considered statistically significant. 16 The treatment with ouabain produced an increase in systolic blood pressure, diastolic blood pressure and mean arterial pressure but did not modify the vascular reactivity to FE, either the endothelial modulation assessed by the percentage of difference of area under the FE curves in the presence and absence of endothelium. The infusion with L-NAME increased vascular reactivity to FE in the two studied groups, but this increase was greater in the group treated with ouabain. This behavior was also observed with the perfusion with TEA, suggesting increased release of NO and EDHF in animals treated with ouabain. The perfusion with indomethacin caused no changes in reactivity, however, co-perfusion with L-NAME and indomethacin increased FE reactivity in the two studied groups. Nevertheless, only in the group treated with ouabain, this increased FE reactivity was smaller than that obtained after perfusion with only L-NAME, suggesting release of vasoconstrictive prostanoids. Treatment with ouabain was also able to promote increase of the KCl relaxation. The administration of nanomolar concentrations of ouabain for 15 days leads to increased systolic, diastolic and average blood pressure, but does not promote change in vascular reactivity in the conductance arteries studied. However, it increases the endothelial release of NO, EDHF and prostanoids vasoconstrictors, in addition to suggesting an increased activity of the sodium pump. Therefore, it is believed that the release of vasodilator and vasoconstrictor factors offset each other, unchanging vascular reactivity. The results of this study suggest changes in the participation of endothelial factors occurs during the onset of arterial hypertension induced by ouabain.