Efeitos do tratamento crônico com ouabaína por 15 dias sobre a contratilidade cardíaca de ratos

• Autor(a) principal: Meira, Eduardo Frizzera
• Data de Publicação: 2009
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
• Texto Completo: http://repositorio.ufes.br/handle/10/7935
• topic: Ouabaína; Hipertensão; Músculo papilar; Ratos; Fisiologia; 612

Ouabain (OUA) is an endogenous compound present in nanomolares concentration in the plasma hypertensive patients, participating of genesis and/or maintenance of the hypertension. The chronic OUA treatment for five week induces hypertension, beyond positive inotropic effect and increased α1 e α2 isoform sodium pump expression in left ventricle of rats. However, studies on ventricular contractility and Na+ -K+ ATPase activity in the initial period of hypertension produced by ouabain are not investigated yet. For this, normotensive rats (Wistar); with 3 months age, were used. The animals were treated daily with vehicle (soybean 0,1ml) or ouabain during 15 days. After the treatment, the animals were anesthetized with urethane (1.2 g/Kg, i.p) and the left carotid artery was cannulated for determination of the mean, systolic and diastolic blood pressure, heart rate, left ventricle systolic, left ventricle end diastolic pressure (LVEDP) and their first time derivatives positive and negative. After the hemodynamic registers, the animals were submitted to thoracotomy and the hearts removed and perfused through the aortic stump to permit a dissection of the left ventricle papillary muscles. The preparation were mounted in a chambers (20ml) contend gassed Krebs-Henseleit solution (26ºC). The following protocols were used: participation of the calcium transsarcolemal flow, the tetanics contractions (TC), the isometric peak force (F), post-rest potentiation in the 15, 30 and 60s (PRP), change in the rate stimulation (CS) and the positive inotropic effect of isoprenaline (ISO). Also were analyzed the Na+ -K+ ATPase (NKA) activity and protein expressions of Na+ /Ca2+ change (NCX), Ca2+ ATPase sarcoplasmic reticulum (SERCA), phospholamban (PBL), AT1 receptor and expression α1 and α2 Na+K +ATPase isoform. The ouabain treated group demonstrated increases the all hemodynamics parameters except in LVEDP. The treatment with OUA reduced isometric peak force (vehicle: 0,56 ± 0,055 vs ouabain:0,35 ± 0,043 p<0,05) and doesn’t modify PRP and TC. Also did not observe alterations in the ISO, calcium transsarcolemal flow and CS. The treatment with OUA increased Na+K +ATPase activity (vehicle: 151,85 ± 7.60 vs ouabain: 191,03 ± 11,41, p<0,05) and reduced expression of the α1 Na+K +ATPase isoform (vehicle: 0,98 ± 0,06 vs ouabain: 0,76 ± 0,06, p<0,05), NCX (vehicle:1,96±0,13 vs ouabain 0,78±0,06, p<0,05) and AT1 receptor (vehicle: 1,19 ± 0,18 vs ouabain: 0,72 ± 0,08, p<0,05) expression when compared with the vehicle group. In conclusion, results demonstrated that chronic ouabain treatment for 15 days, in normotensive rats, produces negative inotropic effect. This effect can be associated with increased Na+K +ATPase activity, reduction of the protein expression of the α1 Na+K +ATPase isoform and reduction protein expression of the NCX. Moreover, the treatment with ouabain reduced protein expression AT1receptor suggesting involvement of central mechanisms like increased sympatoexcitatory activity via activation renin-angiotensin system