Angiotensin-(3–4) (Val-Tyr) 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

Purpose To investigate 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. Methods From 28 to 93 days of age, weaned male Wistar rats were given a diet with low content and poor-quality protein, 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. Results Undernourished rats aged 93 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. SBP was normalized with Losartan and with Ang-(3–4), 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). Conclusions 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 Na + distribution and handling give support to the proposal that Ang IIÞAT 1 R and Ang IIÞAT 2 R axes have opposite roles within the renin-angiotensin-aldosterone system of undernourished juvenile rats.