Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension

Area of Science:

• Cardiovascular Research
• Metabolic Science
• Renal Physiology

Background:

• Hypertension is a key feature of metabolic syndrome, with dietary salt negatively impacting metabolic health.
• Lifestyle modifications like salt reduction and exercise are crucial for managing salt-sensitive hypertension.
• The metabolic effects of salt and exercise on hypertension require further investigation.

Purpose of the Study:

• To investigate the impact of dietary salt on metabolism in a salt-sensitive hypertension model.
• To explore the potential of beta-hydroxybutyrate (βOHB) as a therapeutic target for salt-sensitive hypertension.

Main Methods:

• Utilized an untargeted metabolomic approach in a rat model of salt-sensitive hypertension.
• Administered 1,3-butanediol to supplement beta-hydroxybutyrate (βOHB) levels in high-salt-fed rats.
• Assessed blood pressure, kidney function, and potential mechanisms including gut microbiota, Th17 cells, and renal Nlrp3 inflammasome.

Main Results:

• High salt intake in hypertensive rats led to decreased circulating levels of beta-hydroxybutyrate (βOHB).
• Supplementation with 1,3-butanediol to restore βOHB levels attenuated hypertension and preserved kidney function.
• The beneficial effects of βOHB appeared independent of gut microbiota and Th17 cells, but involved inhibition of the renal Nlrp3 inflammasome.

Conclusions:

• Dietary salt adversely affects metabolism by lowering βOHB levels in salt-sensitive hypertension.
• Restoring βOHB levels through precursor supplementation offers a therapeutic strategy for salt-sensitive hypertension.
• Supplementing βOHB precursors provides benefits comparable to exercise for salt-sensitive hypertension.