Central nervous system mechanisms of salt-sensitive hypertension
Yumei Feng, Shiyue Pan, Himanshu Verma, Haifeng Zheng, Adriana Alviter Plata, Jasenka Zubcevic, Frans H.H. Leenen
Abstract
Salt-sensitive and salt-induced hypertension (SHTN) is a multifaceted and heterogeneous condition influenced by various factors, including lifestyle, genetics, sex, age, and dietary salt intake. Despite its prevalence, affecting about 50% of hypertensive and 25% of normotensive individuals, the precise mechanisms driving salt sensitivity remain incompletely understood. The central nervous system (CNS) plays a pivotal role in SHTN, as it detects changes in plasma and cerebrospinal fluid sodium (Na + ) concentrations and integrates sensory signals from peripheral organs. These inputs, in turn, regulate the autonomic nervous system, leading to an increase in sympathetic nerve activity that contributes to the onset of SHTN. This review examines the CNS mechanisms involved in SHTN, focusing on the key afferent and efferent pathways in its pathogenesis. We summarize recent findings on critical neural circuits activated by dietary salt and examine several key signaling pathways, including the brain’s renin-angiotensin system, aldosterone-“ouabain,” and salt-sensitive G proteins. Additionally, we discuss the clinical relevance of targeting the CNS for SHTN treatment and review current therapeutic approaches.