The pathogenic role of Na(+) in primary hypertension is widely recognized but that of K(+) remains unappreciated. Yet, extensive evidence indicates that together, the body's dominant cations constitute the chief environmental factor in the pathogenesis of hypertension and its cardiovascular sequelae. In this Review, we provide a synthesis of the determinants of Na(+) retention and K(+) loss developing in the body as the Na(+)-rich and K(+)-poor modern diet interacts with kidneys intrinsically poised to conserve Na(+) and excrete K(+); and the molecular pathways utilized by these disturbances in the central nervous system and the periphery to increase sympathetic tone and vascular resistance, and establish hypertension. These fresh insights point to new directions for targeted pharmacotherapy of hypertension. The interdependency of Na(+) and K(+) in the pathogenesis of hypertension indicates that Na(+) restriction and increased K(+) intake are important strategies for the primary prevention and treatment of hypertension and its cardiovascular consequences.
Keywords: Sodium sensitivity; aldosterone; angiotensin II; calcium signaling; endogenous ouabain; potassium channels; sympathetic activity.
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