Purpose of review: Primary hypertension is characterized by Na excess and K deficit in the body, which together are key to its pathogenesis. These derangements work jointly in the brain and the peripheral vascular wall to establish hypertension. In this review, we highlight recent evidence describing the central mechanisms through which Na surfeit and K deficit enhance sympathetic nerve activity, thereby raising peripheral vascular resistance and generating hypertension.
Recent findings: Animal studies point to a small increase in plasma and cerebrospinal fluid (CSF) [Na], a small decrease in CSF [K], and increased levels of circulating angiotensin II, aldosterone, and endogenous ouabain as the central signals evoking hypertension. These signals are detected by circumventricular organ sensors in the forebrain, and are then relayed to hypothalamic nuclei, which project angiotensinergic effector pathways to brainstem nuclei and spinal preganglionic neurons, triggering increased sympathetic nerve activity and hypertension. These central processes depend on a noncirculating (brain) renin-angiotensin-aldosterone system, local production of endogenous ouabain, and increased oxidative stress.
Summary: Recent insights into the mechanisms mediating the central effects of Na excess and K deficit on raising sympathetic activity might pave the way for novel approaches to preventing and treating hypertensive disorders.