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- Title
A Low-Sodium Diet Boosts Ang (1–7) Production and NO-cGMP Bioavailability to Reduce Edema and Enhance Survival in Experimental Heart Failure.
- Authors
Tripathi, Ranjana; Sullivan, Ryan D.; Fan, Tai-Hwang M.; Mehta, Radhika M.; Gladysheva, Inna P.; Reed, Guy L.
- Abstract
Sodium restriction is often recommended in heart failure (HF) to block symptomatic edema, despite limited evidence for benefit. However, a low-sodium diet (LSD) activates the classical renin-angiotensin-aldosterone system (RAAS), which may adversely affect HF progression and mortality in patients with dilated cardiomyopathy (DCM). We performed a randomized, blinded pre-clinical trial to compare the effects of a normal (human-equivalent) sodium diet and a LSD on HF progression in a normotensive model of DCM in mice that has translational relevance to human HF. The LSD reduced HF progression by suppressing the development of pleural effusions (p < 0.01), blocking pathological increases in systemic extracellular water (p < 0.001) and prolonging median survival (15%, p < 0.01). The LSD activated the classical RAAS by increasing plasma renin activity, angiotensin II and aldosterone levels. However, the LSD also significantly up-elevated the counter-regulatory RAAS by boosting plasma angiotensin converting enzyme 2 (ACE2) and angiotensin (1–7) levels, promoting nitric oxide bioavailability and stimulating 3′-5′-cyclic guanosine monophosphate (cGMP) production. Plasma HF biomarkers associated with poor outcomes, such as B-type natriuretic peptide and neprilysin were decreased by a LSD. Cardiac systolic function, blood pressure and renal function were not affected. Although a LSD activates the classical RAAS system, we conclude that the LSD delayed HF progression and mortality in experimental DCM, in part through protective stimulation of the counter-regulatory RAAS to increase plasma ACE2 and angiotensin (1–7) levels, nitric oxide bioavailability and cGMP production.
- Subjects
NEPRILYSIN; ANGIOTENSIN converting enzyme; HEART failure; RENIN-angiotensin system; ANGIOTENSIN II; BIOAVAILABILITY; GUANYLIC acid
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 8, p4035
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22084035