Rostafuroxin, the inhibitor of endogenous ouabain, ameliorates chronic undernutrition-induced hypertension, stroke volume, cardiac output, left-ventricular fibrosis and alterations in Na+-transporting ATPases in rats.

Our aim has been to investigate the effect of Rostafuroxin, an inhibitor of endogenous cardiotonic steroids (EO/CTS), on cardiac structure and function and cardiac Na+ transport in undernourished hypertensive Wistar rats, and to determine whether chronic undernutrition is a modifiable risk factor for cardiovascular-kidney-metabolic (CKM) syndrome. Echocardiographic studies evaluated stroke volume cardiac output, ejection fraction, mitral valve early diastolic blood flow/late diastolic blood flow (E/A) ratio, and right renal resistive index. The cardiomyocyte area and collagen infiltration of cardiac tissue were investigated, as also the activities of the cardiac ouabain-sensitive (Na++K+)ATPase ((Na++K+)ATPase Sens) and ouabain-resistant Na+-ATPase (Na+-ATPase Res). Undernourished hypertensive rats presented tachycardia, reduced stroke volume, decreased cardiac output, preserved fractional shortening and ejection fraction, unmodified mitral valve E/A ratio, and increased right renal resistive index. Cardiomyocyte size decreased and intense collagen infiltration had occurred. The (Na++K+)ATPase Sens activity decreased, whereas that of Na+-ATPase Res increased. Rostafuroxin selectively modified some of these echocardiographic and molecular parameters: it increased stroke volume and cardiac output and prevented histopathological alterations. The drug decreased and increased the activities of (Na++K+)ATPase Sens and Na+-ATPase Res, respectively, in normonourished rats, and the opposite trend was found in the undernourished group. It is concluded that chronic undernutrition in rats can provoke structural, functional, histological, and molecular cardiovascular alterations that, with the simultaneous changes in renal parameters described in this and in previous studies, configure an undescribed type of CKM syndrome. The data also demonstrate that the blockade of EO/CTS ameliorates stroke volume and cardiac output, thus preventing or delaying the worsening of the syndrome.