Salt-sensing mechanisms in blood pressure regulation and hypertension.
High salt consumption contributes to the development of hypertension and is considered an independent risk factor for vascular remodeling, cardiac hypertrophy, and stroke incidence. In this review, we discuss the molecular origins of primary sensors involved in the phenomenon of salt sensitivity. Based on the analysis of literature data, we conclude that the kidneys and central nervous system (CNS) are two major sites for salt sensing via several distinct mechanisms: 1) [Cl(-)] sensing in renal tubular fluids, primarily by Na(+)-K(+)-Cl(-) cotransporter (NKCC) isoforms NKCC2B and NKCC2A, whose expression is mainly limited to macula densa cells; 2) [Na(+)] sensing in cerebrospinal fluid (CSF) by a novel isoform of Na(+) channels, Na(x), expressed in subfornical organs; 3) sensing of CSF osmolality by mechanosensitive, nonselective cation channels (transient receptor potential vanilloid type 1 channels), expressed in neuronal cells of supraoptic and paraventricular nuclei; and 4) osmolarity sensing by volume-regulated anion channels in glial cells of supraoptic and paraventricular nuclei. Such multiplicity of salt-sensing mechanisms likely explains the differential effects of Na(+) and Cl(-) loading on the long-term maintenance of elevated blood pressure that is documented in experimental models of salt-sensitive hypertension.
Orlov
Sergei N
SN
Department of Medicine and Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada. sergei.n.orlov@umontreal.ca
Mongin
Alexander A
AA
D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000134:cerebrospinal fluid / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction; D015222:Sodium Channels / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D013495:Supraoptic Nucleus / Q000378:metabolism / Q000503:physiopathology; D050916:TRPV Cation Channels / Q000378:metabolism; D014882:Water-Electrolyte Balance
C578714:SLC12A1 protein, human; D015222:Sodium Channels; D017673:Sodium Chloride, Dietary; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D050916:TRPV Cation Channels