Low-dose ouabain administration increases Na+,K+-ATPase activity and reduces cardiac force development in rats

Background: Ouabain is a digitalis compound that inhibits the Na+,K+-ATPase (NKA) activity inducing increment in cardiac force. However, this effect seems to be dose dependent. At low concentration, ouabain can induce an increase of NKA activity. Methods: We investigated the effects of ouabain administration (25 mu g/kg/day) for 15 days on cardiac contractility and NKA activity. Blood pressure and left ventricular papillary muscle contraction from placebo and ouabain-treated rats for 15 (OUA15) days were evaluated. Isometric force, post-rest potentiation, positive inotropic intervention produced by isoproterenol, and tetanic tension were measured. The activity and protein expression levels of alpha 1 and alpha 2 isoforms of NKA, sodium calcium exchanger (NCX), sarcoplasmic reticulum calcium ATPase (SERCA2a) and phospholamban (PLB) were also measured. Results: Systolic and diastolic blood pressures increased after treatment with ouabain. However, isometric tension was reduced in the ouabain treated group. Post-rest potentiation, time parameters, inotropic interventions by isoproterenol and tetanic tension did not change. In the ouabain treated group, NKA activity was increased (Oua 406.16 +/- 70.6 vs. CT 282.80 +/- 80.5) while protein expression of the alpha 1 isoform of NKA was reduced (Oua 0.97 +/- 0.06 vs. CT 0.76 +/- 0.05). No changes were observed in protein expression of alpha 2 isoform of NKA, NCX, SERCA2a and PLB. Therefore, although 15-day ouabain treatment increases blood pressure (Oua: 116.4 +/- 3 vs. CT: 99.9 +/- 3), treatment also reduces isometric tension development (Oua: 0.34 +/- 0.14 vs. CT: 0.56 +/- 0.22). Conclusion: We suggest that the effects induced by ouabain in the isolated cardiac muscle could be related at least in part, to changes in NKA activity. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.