Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, PC192
Differences in ouabain-sensitive Na+-K+-ATPase activity in aorta following myocardial infarction
I. Stefanon1, F. M. Vargas1, P. P. Cappato1, A. C. Davel2, R. F. Ribeiro Junior1, A. A. Fernandes1, D. V. Vassallo1, L. V. Rossoni2
1. Ciencias Fisiologicas, Universidade Federal do Espirito Santo, Vitoria, ES, Brazil. 2. Ciencias Fisiol?gicas, Universidade de S?o Paulo, S?o Paulo, Brazil.
Myocardial infarction (MI) may induce heart failure in rats followed by modification on vascular reactivity and endothelium dysfunction (Ledoux et al. 2003; Pereira et al. 2005). The enzyme Na+-K+-ATPase is responsible for the maintenance of cellular membrane potential and can contribute to the regulation of vascular tone and contractility (Blaustein, 1993). The aim of the present study was to investigate the ouabain-sensitive Na+-K+-ATPase functional activity, and protein expression, in aortic rings of rats with similar infarct size, with and without signals of heart failure. All animals were treated in accordance with the guide for the care and use of laboratory animals published by the US National Institutes of Health. The protocol was approved by a regional animal care and ethics committee. Wistar rats (220 ± 8 g), were distributed in sham-operated (Sham, n=13), infarct without signals of heart failure (Inf, n=11) and infarct with signals of heart failure (HF, n=7). MI was surgically induced (under ketamine (50 mg/kg) and xylazine (10 mg/kg) anaesthesia, i.m.) by occluding the left coronary artery. After 30 days, the rats were anaesthetized (1.2g/kg i.p. urethane), and the aortic rings (4 mm) were superfused with Krebs solution gassed with 95% O2-5% CO2 to study rings with intact endothelium (E+), denuded endothelium (E-) and with L-NAME. The ouabain-sensitive Na+-K+-ATPase functional activity was analysed using the potassium relaxation technique. No differences were observed in the scar size (Inf: 34.2 ± 1.6%; HF: 35.6 ± 2.8%), body weight (Sham: 236 ± 4 g; Inf: 236 ± 5 g; HF: 235 ± 5 g) and left ventricle/body weight ratio (Sham: 2.12 ± 0.05; Inf: 2.24 ± 0.06; HF: 2.21 ± 0.07 mg/g). However, the signals of heart failure appeared only in the HF groups (right ventricle/body weight ratio (Sham: 0.6 ± 0,02; Inf: 0.6 ± 0.03; HF: 1.4 ± 0.1 mg/g*, *P<0.05) and lung weight/body weight ratio (Sham: 5.7 ± 0,3; Inf: 6.1 ± 0.3; HF: 13.6 ± 1.0 mgg*, *P<0.05). The main results of this study are that in the Inf animals the KCl-induced relaxation was diminished and the endothelial modulation of this relaxation, for nitric oxide, was present. However, the capacity of the ouabain to inhibit the Na+-K+-ATPase was increased in these animals and it did not present endothelial modulation as seen in the Sham and HF groups. These results demonstrate that ouabain-dependent NO release is absent in the Inf group, but preserved in the HF. Therefore, the results demonstrate the participation of the Na+-K+-ATPase in the changes of vascular reactivity following myocardial infarction. The identification of two distinct experimental groups after MI in rats, despite a similar infarct size, with and without signals of HF, could explain, at least in part, the contradictory cardiovascular results in experimental models of HF.
Where applicable, experiments conform with Society ethical requirements