Angiotensin-(3-4) normalizes blood pressure, decreases Na+ and energy intake, but preserves urinary Na+ excretion in overweight hypertensive rats

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1867

Article

Luzes, Rafael^1,2  Crisostomo, Thuany³  Silva, Paulo A.²  Iack, Roxane²  de Abreu, Virginia Genelhu²  Francischetti, Emilio A.²  Vieyra, Adalberto^1,2,4 

[1] Univ Fed Rio de Janeiro, Carlos Chagas Filho Inst Biophys, Rio De Janeiro, Brazil

[2] Univ Grande Rio, Grad Program Translat Biomed, Duque De Caxias, RJ, Brazil

[3] Univ Fed Rio de Janeiro, Leopoldo de Meis Inst Med Biochem, Rio De Janeiro, Brazil

[4] Univ Fed Rio de Janeiro, Natl Ctr Struct Biol & Bioimaging CENABIO, Rio De Janeiro, Brazil

关键词: Obesity-associated hypertension;    Renin-angiotensin system;    Angiotensin-(3-4);    Sodium accumulation;    Sodium-transporting ATPases;   

DOI  :  10.1016/j.bbadis.2020.166012

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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