Epidemiologic studies have shown convincingly that drastically reducing salt intake in the community is accompanied by blood pressure reductions that are comparable to those achieved by antihypertensive medication. Moreover, many subjects with hypertension are salt sensitive. This implies that, in these subjects, blood pressure is more responsive to changes in salt intake than in subjects with normal blood pressure. The presence of conventional risk factors associated with the metabolic syndrome correlates with salt sensitivity. However, women appear to be more salt sensitive than men. Sparse data indicate that the salt sensitivity of blood pressure is greater in subjects with low birth weight. Experimental studies in rats have also shown that hypertensive offspring of dams maintained on low-protein diets throughout or in late pregnancy are more salt sensitive. This is accompanied by increased expression of the thick ascending limb Na-K-2Cl symporter (NKCC2). Perinatal interventions aimed at persistently lowering blood pressure in genetically hypertensive rats have consistently proven to be very effective and are often accompanied by a wave of natriuresis exclusively at 4 wk of age. In sum, in addition to conventional metabolic risk factors for cardiovascular disease, low birth weight and possibly its sequels such as catch-up growth should be viewed as modifiable risk factors for salt sensitivity of blood pressure. Female sex may also be a nonmodifiable risk factor for salt sensitivity. Experimental data indicate that NKCC2 may well be an important determinant of salt sensitivity in acquired (developmental) hypertension.
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