Inverse Salt Sensitivity of Blood Pressure: Mechanisms and Potential Relevance for Prevention of Cardiovascular Disease

Abstract

Purpose of review: To review the etiology of inverse salt sensitivity of blood pressure (BP).

Recent findings: Both high and low sodium (Na⁺) intake can be associated with increased BP and cardiovascular morbidity and mortality. However, little is known regarding the mechanisms involved in the increase in BP in response to low Na⁺ intake, a condition termed inverse salt sensitivity of BP, which affects approximately 15% of the adult population. The renal proximal tubule is important in regulating up to 70% of renal Na⁺ transport. The renin-angiotensin and renal dopaminergic systems play both synergistic and opposing roles in the regulation of Na⁺ transport in this nephron segment. Clinical studies have demonstrated that individuals express a "personal salt index" (PSI) that marks whether they are salt-resistant, salt-sensitive, or inverse salt-sensitive. Inverse salt sensitivity results in part from genetic polymorphisms in various Na⁺ regulatory genes leading to a decrease in natriuretic activity and an increase in renal tubular Na⁺ reabsorption leading to an increase in BP. This article reviews the potential mechanisms of a new pathophysiologic entity, inverse salt sensitivity of BP, which affects approximately 15% of the general adult population.

Keywords: Angiotensin; Angiotensin receptor; Dopamine; Dopamine receptor; Inverse salt sensitivity; Renin; Salt sensitivity.