September 5, 2019

How salt increases blood pressure

Vanderbilt researchers have discovered that a protein called SGK1 in immune cells is activated by sodium, leading to the development of salt-sensitive hypertension.

Salt-sensitive hypertension affects about half of people with high blood pressure, but the precise mechanism of how dietary salt contributes to blood pressure elevation, kidney injury and cardiovascular disease remains unclear.

Annet Kirabo, DVM, MSc, PhD, and colleagues recently found that sodium enters immune system antigen-presenting cells (APCs) and promotes formation of IsoLG (isolevuglandin)-protein adducts, leading to inflammation and hypertension. They have now discovered that the salt-sensing kinase SGK1 plays a key role in this pathway.

They found that in response to excessive salt, SGK1 increases expression and assembly of epithelial sodium channels on APCs. This increases activation of NADPH oxidase, an enzyme that participates in IsoLG formation. Mice lacking SGK1 in APCs were protected from kidney inflammation and vascular dysfunction, and had less hypertension associated with a high-salt diet.

The findings, reported in the September issue of Hypertension, define a novel pathway for salt-sensitive hypertension and suggest that SGK1 may be an important therapeutic target for this condition.

This research was supported by the American Heart Association and the National Institutes of Health (grants HL142937, HL130497).