Na+/K+-ATPase α isoforms expression in stroke-prone spontaneously hypertensive rat heart ventricles:: Effect of salt loading and lacidipine treatment

Changes in myocardial expression of Na+/K+-ATPase alpha-subunit isoforms have been demonstrated in different models of cardiac hypertrophy and hypertension. Here we studied the expression of these isozymes in stroke-prone spontaneously hypertensive rats (SHRSP) and the influence of high salt diet and treatment with the dihydropyridine lacidipine. Adult SHRSP were offered either 1% NaCl or water as drinking solution for 6 weeks. Salt-loaded SHRSP were treated or not with I mg/kg/day lacidipine. Compared to Wistar Kyoto (WKY) rats, non-salt-loaded SHRSP presented significant hypertension and cardiac hypertrophy. Salt intake markedly enhanced cardiac hypertrophy, an effect blunted by lacidipine. [H-3]Ouabain binding assays on total particulate fractions from heart ventricles revealed the existence of two high-affinity sites with K-d similar to 25 and similar to 200 nM, ascribed to the alpha(3) and alpha(2) isoforms, respectively. B-max of alpha(3) was unexpectedly high (40% of total high-affinity binding) in ventricles from WKY rats but very low in all groups of SHRSP. On the other hand, B-max of alpha(2) was similar in WKY and non-salt-loaded SHRSP; however, salt loading of SHRSP resulted in a B-max reduction of 20% (P < 0.05), an effect blocked by lacidipine. These effects were largely confirmed by inummoblotting analysis, which, in addition, demonstrated that the density of the ubiquitous (x, isoform was comparable among the experimental groups. In conclusion, WKY rats showed a high myocardial expression of the Na+/K+-ATPase alpha(3) subunit, which was not found in SHRSP; the level of the alpha(2) isoform was similar in untreated SHRSP and WKY, salt-loading of SHRSP promoted reduction of the a, isoform, and this effect was completely hampered by lacidipine. (c) 2007 Elsevier B.V. All rights reserved.