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Inverse Salt Sensitivity of Blood Pressure Is Associated with an Increased Renin-Angiotensin System Activity
John J Gildea1, Peng Xu1, Katie A Schiermeyer1
1Department of Pathology, The University of Virginia, Charlottesville, VA 22903, USA.
Biomedicines
|November 11, 2022
Summary
Inverse salt sensitivity (ISS) involves elevated blood pressure on low-sodium diets. Genetic variants in DRD2 and SLC5A11 genes in kidney cells may explain this paradoxical response and contribute to hypertension.
Area of Science:
- Cardiovascular Science
- Nephrology
- Genetics
Background:
- High and low sodium diets impact blood pressure and cardiovascular health.
- Inverse salt sensitivity (ISS), elevated blood pressure on low-salt diets, affects 11% of adults with unknown causes.
Purpose of the Study:
- Investigate the etiology of ISS.
- Identify cellular mechanisms underlying the paradoxical response to low sodium intake.
Main Methods:
- Analyzed single nucleotide polymorphisms (SNPs) in DRD2 and SLC5A11 genes.
- Examined gene expression in urine-derived renal proximal tubule cells (uRPTCs).
- Utilized cell culture under low sodium conditions, miRNA blocker transfection, and Angiotensin-II stimulation.
Main Results:
- Found a correlation between SNPs in DRD2 and SLC5A11 and decreased gene expression in ISS patients' uRPTCs.
- Demonstrated that low sodium conditions reveal distinct uRPTC physiology in ISS, reversible by DRD2 re-expression.
- Showed that Angiotensin-II increases sodium transport more in ISS uRPTCs, linked to reduced NRF2, CTCF, and SOD2 expression.
Conclusions:
- Genetic variants in DRD2 and SLC5A11 may contribute to ISS by increasing sensitivity to Angiotensin-II and renal sodium reabsorption.
- These findings offer insight into the pathophysiology of inverse salt-sensitive hypertension.
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