Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Undernutrition Modifies the Antihypertensive and Metabolic Responses of Rostafuroxin in Male Rats: Outcomes on Bodily Na+ Handling and Renal Na+-transporting ATPases

Version 1 : Received: 17 May 2023 / Approved: 17 May 2023 / Online: 17 May 2023 (10:58:02 CEST)

How to cite: Pereira-Acácio, A.; Veloso-Santos, J.P.; Veloso-Santos, J.P.; Costa-Sarmento, G.; Muzi-Filho, H.; Vieyra, A. Undernutrition Modifies the Antihypertensive and Metabolic Responses of Rostafuroxin in Male Rats: Outcomes on Bodily Na+ Handling and Renal Na+-transporting ATPases. Preprints 2023, 2023051242. https://doi.org/10.20944/preprints202305.1242.v1 Pereira-Acácio, A.; Veloso-Santos, J.P.; Veloso-Santos, J.P.; Costa-Sarmento, G.; Muzi-Filho, H.; Vieyra, A. Undernutrition Modifies the Antihypertensive and Metabolic Responses of Rostafuroxin in Male Rats: Outcomes on Bodily Na+ Handling and Renal Na+-transporting ATPases. Preprints 2023, 2023051242. https://doi.org/10.20944/preprints202305.1242.v1

Abstract

The aim of the present study was to investigate whether chronic undernutrition modifies the response to rostafuroxin in juvenile rats. Chronic undernutrition was induced in male rats using a multideficient diet known as 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) or vehicle were orally administered during the last 30 days. Undernourished rats became hypertensive at 55–60 days of age (tail-cuff recording). During the last two days, the rats were hosted in metabolic cages to measure food/energy, water, Na+ ingestion, and urinary volume. Blood and kidneys were collected after euthanasia. Rostafuroxin increased food/energy and Na+ intake in CTRL and RBD rats but had opposite effects on Na+ balance (intake minus urinary excretion): negative in CTRL and positive in RBD. The drug normalized the decreased plasma Na+ concentration found 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, furosemide-sensitive 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, caloric metabolism, Na+ distribution in liquid compartments, mobilization of Na+ from non-osmotic compartments, Na+ and water balance, and activity of renal Na+-transporting ATPases to rostafuroxin.

Keywords

rostafuroxin; arterial hypertension; chronic undernutrition; Regional Basic Diet; sodium and water balance; renal Na+-transporting ATPases

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

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