Salt sensitivity of blood pressure: mechanisms and sex-specific differences

Abstract

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular disease in individuals with or without hypertension. However, the mechanisms and management of SSBP remain unclear, mainly because the diagnosis of this condition relies on salt loading–depletion protocols that are not feasible in the clinic. The prevalence of hypertension is lower in premenopausal women than in men, but this sex-specific difference is reversed after menopause. Whether excessive SSBP in women at any age contributes to this reversal is unknown, but many clinical studies that have rigorously assessed for SSBP using salt loading–depletion protocols have confirmed that SSBP is more prevalent in women than in men, including during premenopausal age. In this Review, we discuss sex-specific mechanisms of SSBP. We describe sex-related differences in renal transporters, hypertensive pregnancy, SSBP in autoimmune disorders and mitogen-activated protein kinase signalling pathways, and highlight limitations and lessons learned from Dahl salt-sensitive rat models. In this Review, Kirabo and colleagues discuss the mechanisms that underlie the sex-related differences in salt sensitivity of blood pressure and hypertension, highlighting the implications for research and clinical practice.