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

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⁺ (U_NaV) remained unmodified. The preservation of U_NaV 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.

Keywords: Angiotensin-(3–4); Obesity-associated hypertension; Renin-angiotensin system; Sodium accumulation; Sodium-transporting ATPases.