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⇒AT(1)R and Ang II⇒AT(2)R axes have opposite roles within the renin-angiotensin-aldosterone system of undernourished juvenile rats.