Transforming growth factor-β mediates endothelial dysfunction in rats during high salt intake

Area of Science:

• Cardiovascular Science
• Renal Physiology
• Molecular Biology

Background:

• Endothelial dysfunction predicts cardiovascular events.
• High salt intake promotes endothelial dysfunction via unknown mechanisms.
• Transforming growth factor-beta (TGF-β) may link salt intake to endothelial dysfunction and blood pressure.

Purpose of the Study:

• To test if dietary salt-induced TGF-β promotes endothelial dysfunction.
• To investigate TGF-β's role in salt-dependent blood pressure changes.

Main Methods:

• Sprague-Dawley rats fed low salt (0.3% NaCl) or high salt (8.0% NaCl) diets.
• Treatment with vehicle or a TGF-β receptor I inhibitor (SB-525334).
• Blood pressure monitored via radiotelemetry; endothelial function and molecular markers assessed.

Main Results:

• High salt intake increased systolic blood pressure and pulse pressure.
• Endothelium-dependent vasorelaxation was impaired in high salt-fed rats.
• Inhibiting TGF-β signaling normalized blood pressure and endothelial function, reducing phospho-Smad2 and NADPH oxidase-4.

Conclusions:

• Dietary salt-induced endothelial dysfunction and blood pressure increases are linked to TGF-β signaling.
• TGF-β pathway inhibition offers a potential therapeutic strategy for salt-sensitive hypertension.