Role of Na+/K+-ATPase in the high extracellular calcium-induced impairment of rabbit aorta contractile activity

The present study was designed to prove whether the activation of the sarcolemmal Na+/K+-ATPase in the rabbit aorta could explain the decreased contraction caused in this tissue by high extracellular calcium. To demonstrate this hypothesis, we evaluate the modification in the contractile responses to KCl and alpha(1)-adrenoceptor agonists (methoxamine and phenylephrine) produced by a high extracellular Ca2+ concentration (10 mM) in isolated rabbit aorta rings when the Na+/K+-ATPase is inhibited with ouabain. Ouabain 10(-4) M caused an initial rapid increase in tone in the rabbit aorta rings, which could be linked to the release of catecholamines provoked when the Na+/K+-ATPase in the nerve terminal was blocked. This glycoside also caused a delayed contractile response in the preparations that could be linked to the inhibition of the Na+/K+-ATPase in the sarcolemma of the smooth muscle. The maximum inhibition of the sarcolemmal pump was fixed 2 h and 15 min after ouabain 10(-4) M administration. Both responses were smaller with the 10-mM Ca2+ concentration than with the 2.5-mM Ca2+ concentration. The contractions elicited by KCl and the alpha(1)-adrenoceptor agonists were higher in the aorta ring preparations incubated with the 2.5-mm Ca2+ solution than in the aorta ring preparations incubated with the 10-mM Ca2+ solution. When the Ca2+ concentration in the organ bath was 2.5 mM, 10(-4) M ouabain administration caused a decrease in the responses to KCl and alpha(1)-adrenoceptor agonists. By contrast, when the Ca2+ concentration in the organ bath was 10 mM, 10(-4) M ouabain did not modify these responses. As a consequence, the contractions elicited by KCl were very similar in all the ouabain-treated preparations and those elicited by the alpha(1)-adrenoceptor agonists in ouabain-treated preparations were even higher when the Ca2+ concentration in the organ bath was 10 mM than when the Ca2+ concentration in the organ bath was 2.5 mM. The results of this study suggest that the increase in extracellular Ca2+ concentration may facilitate the functioning of the Na+/K+-ATPase in the vascular smooth muscle (VSM) and produces opposite effects to ouabain. This effect of high extracellular Ca2+ concentration on the sarcolemmal pump may explain the decrease in the contractile responses elicited by depolarization and alpha(1)-adrenoceptor stimulation observed in rabbit aorta ring preparations. (C) 2004 Elsevier Inc. All rights reserved.