Salt, Na+,K+-ATPase and hypertension.
Chronic hypertension is characterized by a persistent increase in vascular tone. Sodium-rich diets promote hypertension; however, the underlying molecular mechanisms are not fully understood. Variations in the sodium content of the diet, through hormonal mediators such as dopamine and angiotensin II, modulate renal tubule Na(+),K(+)-ATPase activity. Stimulation of Na(+),K(+)-ATPase activity increases sodium transport across the renal proximal tubule epithelia, promoting Na(+) retention, whereas inhibited Na(+),K(+)-ATPase activity decreases sodium transport, and thereby natriuresis. Diets rich in sodium also enhance the release of adrenal endogenous ouabain-like compounds (OLC), which inhibit Na(+),K(+)-ATPase activity, resulting in increased intracellular Na(+) and Ca(2+) concentrations in vascular smooth muscle cells, thus increasing the vascular tone, with a corresponding increase in blood pressure. The mechanisms by which these homeostatic processes are integrated in response to salt intake are complex and not completely elucidated. However, recent scientific findings provide new insights that may offer additional avenues to further explore molecular mechanisms related to normal physiology and pathophysiology of various forms of hypertension (i.e. salt-induced). Consequently, new strategies for the development of improved therapeutics and medical management of hypertension are anticipated.
Jaitovich
Ariel
A
Membrane Signaling Networks, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital-Solna, 171 76 Stockholm, Sweden. ajaitovich@ccbhs.org
Bertorello
Alejandro M
AM
D000818:Animals; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D010042:Ouabain / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000009:adverse effects* / Q000493:pharmacokinetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014655:Vascular Resistance / Q000187:drug effects
D017673:Sodium Chloride, Dietary; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase