How NaCl raises blood pressure: a new paradigm for the pathogenesis of salt-dependent hypertension

摘要: Excess dietary salt is a major cause of hypertension. Nevertheless, the specific mechanisms by which increases arterial constriction and peripheral vascular resistance, thereby raises blood pressure (BP), are poorly understood. Here we summarize recent evidence that defines molecular links between Na+ elevated resistance directly produces high BP. In this new paradigm, cerebrospinal fluid [Na+]. This leads, via Na+-sensing circumventricular organs brain, to increased sympathetic nerve activity (SNA), trigger vasoconstriction. Plasma levels endogenous ouabain (EO), pump ligand, also become elevated. Remarkably, [Na+]-evoked, locally secreted (hypothalamic) EO participates in pathway mediates sustained increase SNA. hypothalamic signaling chain includes aldosterone, epithelial channels, EO, ouabain-sensitive α2 pumps, angiotensin II (ANG II). The (e.g.) ANG-II type-1 receptor NADPH oxidase decreases neuronal nitric oxide synthase protein expression. aldosterone-epithelial channel-EO-α2 pump-ANG-II modulates brain cardiovascular control centers regulate BP set point induce changes periphery, adrenal cortex enhances vasoconstriction an EO-α2 pump-Na+/Ca2+ exchanger-Ca2+ pathway. Circulating activates pump-Src kinase cascade. expression Na+/Ca2+ exchanger-transient potential cation channel Ca2+ smooth muscle but endothelial vasodilator mechanisms. Additionally, growth factor may participate structural remodeling lumen narrowing frequently observed established These several central coordinated, part effect maintain salt-induced elevation