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

PLoS One. 2022 Aug 19;17(8):e0273385. doi: 10.1371/journal.pone.0273385. eCollection 2022.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Angiotensin II* / pharmacology
  • Animals
  • Arterial Pressure
  • Blood Pressure
  • Losartan / pharmacology
  • Male
  • Malnutrition* / complications
  • Rats
  • Rats, Wistar
  • Receptors, Angiotensin / metabolism
  • Sodium / metabolism

Substances

  • Receptors, Angiotensin
  • Angiotensin II
  • Sodium
  • Adenosine Triphosphatases
  • Losartan

Grants and funding

This work is supported by Brazilian Research Council/CNPq (https://www.gov.br/cnpq/pt-br, grants 470266/2014-7 and 440544/2018-1 to AV), Rio de Janeiro State Foundation/FAPERJ (https://www.faperj.br/, grants E- 26/210.890/2019 and E-26/201.909/2020 to AV), and the Brazilian Federal Agency for Support and Evaluation of Graduate Education/CAPES (https://www.gov.br/capes/pt-br, grants 88887.124150/2014-00 to AV, 88887.320213/2019-00 to HM-F, 88887.374390/2019-00 to AP-A and 88887.634142/2021-00 to AP-A). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.