Horacio J. Adrogué

International guidelines designed to minimize the risk of complications that can occur when correcting severe hyponatremia have been widely accepted for a decade. On the basis of the results of a recent large retrospective study of patients hospitalized with hyponatremia, it has been suggested that hyponatremia guidelines have gone too far in limiting the rate of rise of the serum sodium concentration; the need for therapeutic caution and frequent monitoring of the serum sodium concentration has been questioned. These assertions are reminiscent of a controversy that began many years ago. After reviewing the history of that controversy, the evidence supporting the guidelines, and the validity of data challenging them, we conclude that current safeguards should not be abandoned. To do so would be akin to discarding your umbrella because you remained dry in a rainstorm. The authors of this review, who represent 20 medical centers in nine countries, have all contributed significantly to the literature on the subject. We urge clinicians to continue to treat severe hyponatremia cautiously and to wait for better evidence before adopting less stringent therapeutic limits.

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. 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. 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.