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Biochim Biophys Acta Mol Basis Dis ; 1867(3): 166012, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33212189

ABSTRACT

Hypertension, one of the most common and severe comorbidities of obesity and overweight, is a worldwide epidemic affecting over 30% of the population. We induced overweight in young male rats (aged 58 days) by exposure to a hypercaloric high lipid (HL) diet in which 70% of the calories originated from fat. The HL diet also contained 33 or 57% higher Na+ than the control (CTR) diet. Over the following weeks the HL rats gradually became overweight (490 ± 12 g vs 427 ± 7 g in the CTR group after 15 weeks) with high visceral fat. They developed elevated systolic blood pressure (SBP) (141 ± 1.9 mmHg), which was fully restored to CTR values (128 ± 1.1 mmHg) by oral administration of Ang-(3-4) (Val-Tyr), the shortest renin-angiotensin-derived peptide. The overweight rats had lower plasma Na+ concentration that augmented to CTR values by Ang-(3-4) treatment. Na+ ingestion was depressed by 40% as result of the Ang-(3-4) treatment, whereas the urinary excretion of Na+ (UNaV) remained unmodified. The preservation of UNaV after Ang-(3-4) treatment - despite the sharp decrease in the dietary Na+ intake - can be ascribed to the normalization of renal type 1 angiotensin II receptors and Na+-transporting ATPases, both up-regulated in overweight rats. These renal effects complete a counterregulatory action on elevated renin-angiotensin activity that allows the high SBP to be normalized and body Na+ homeostasis to be restored concomitantly in overweight rats.


Subject(s)
Angiotensins/therapeutic use , Blood Pressure/drug effects , Energy Intake/drug effects , Hypertension/drug therapy , Overweight/drug therapy , Peptide Fragments/therapeutic use , Animals , Hypertension/complications , Hypertension/physiopathology , Hypertension/urine , Male , Overweight/complications , Overweight/physiopathology , Overweight/urine , Rats , Rats, Wistar , Sodium/metabolism , Sodium/urine
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