Different antihypertensive and metabolic responses to rostafuroxin in undernourished and normonourished male rats: Outcomes on bodily Na+ handling.

Hypertension is a pandemic nowadays. We aimed to investigate whether chronic undernutrition modifies the response to the antihypertensive drug rostafuroxin in juvenile hypertensive rats. Chronic undernutrition was induced in male rats using a multideficient diet known as the Regional Basic Diet (RBD), mimicking alimentary habits in impoverished regions worldwide. Animals were given RBD-or a control/CTRL normal diet for rodents-from weaning to 90 days, and rostafuroxin (1 mg/kg body mass) was orally administered from day 60 onwards. For the last 2 days, the rats were hosted in metabolic cages to measure food/energy, water, Na+ ingestion, and urinary volume. Rostafuroxin increased food/energy/Na+ intake in CTRL and RBD rats but had opposite effects on Na+ balance (intake minus urinary excretion). The drug normalized the decreased plasma Na+ concentration in RBD rats, increased urinary volume in RBD but not in CTRL, and decreased and increased urinary Na+ concentration in the RBD and CTRL groups, respectively. Rostafuroxin decreased the ouabain-sensitive (Na+ +K+ )ATPase and increased the ouabain-resistant Na+ -ATPase from proximal tubule cells in both groups and normalized the systolic blood pressure in RBD without effect in CTRL rats. We conclude that chronic undernutrition modifies the response of blood pressure and metabolic responses to rostafuroxin.

Angiotensin-(3-4) normalizes the elevated arterial blood pressure and abnormal Na+/energy handling associated with chronic undernutrition by counteracting the effects mediated by type 1 angiotensin II receptors.

We investigated the mechanisms by which chronic administration of a multideficient diet after weaning alters bodily Na+ handling, and culminates in high systolic blood pressure (SBP) at a juvenile age. From 28 to 92 days of age, weaned male Wistar rats were given a diet with low content and poor-quality protein, and low lipid, without vitamin supplementation, which mimics the diets consumed in impoverished regions worldwide. We measured food, energy and Na+ ingestion, together with urinary Na+ excretion, Na+ density (Na+ intake/energy intake), plasma Na+ concentration, SBP, and renal proximal tubule Na+-transporting ATPases. Undernourished rats aged 92 days had only one-third of the control body mass, lower plasma albumin, higher SBP, higher energy intake, and higher positive Na+ balance accompanied by decreased plasma Na+ concentration. Losartan or Ang-(3-4) normalized SBP, and the combination of the 2 substances induced an accentuated negative Na+ balance as a result of strong inhibition of Na+ ingestion. Na+ density in undernourished rats was higher than in control, irrespective of the treatment, and they had downregulated (Na++K+)ATPase and upregulated Na+-ATPase in proximal tubule cells, which returned to control levels after Losartan or Ang-(3-4). We conclude that Na+ density, not only Na+ ingestion, plays a central role in the pathophysiology of elevated SBP in chronically undernourished rats. The observations that Losartan and Ang-(3-4) normalized SBP together with negative Na+ balance give support to the proposal that Ang II⇒AT1R and Ang II⇒AT2R axes have opposite roles within the renin-angiotensin-aldosterone system of undernourished juvenile rats.