Contributions of Sodium and Chloride to NaCl-Induced Hypertension

Abstract

The recommendation to avoid high dietary “salt” intake for the prevention and treatment of hypertension is often expressed in terms of dietary sodium. However, a consistent body of evidence suggests that the chloride component of salt is an important contributor to NaCl-induced elevations of blood pressure.1 In several rat models of salt-sensitive hypertension (Dahl salt-sensitive [S] rat, DOCA-salt hypertension, stroke-prone SHR [SHRSP], angiotensin II-induced salt-sensitive hypertension), selective dietary sodium loading, in the absence of chloride, fails to produce hypertension. In various feeding protocols, anions provided with sodium included various combinations of bicarbonate, phosphate, aspartate, glutamate, and glycinate. Overall, the failure of selective dietary sodium loading to produce hypertension in these studies was not related to group differences of body weight, net sodium balance, blood pH, or serum concentrations of sodium, potassium, or chloride. Similarly, a limited number of clinical observations also indicate that blood pressure is not increased in humans by high dietary sodium intakes in the absence of chloride. In 1929, Berghoff et al reported that blood pressure increased in 7 hypertensive individuals on a high NaCl intake, but not on a high sodium bicarbonate intake.2 This observation was subsequently confirmed.3 Similarly, other investigators have also observed that in contrast to the increase of blood pressure induced by a high NaCl intake in hypertensive patients, blood pressure is not increased by a high sodium intake provided as sodium phosphate or sodium citrate.1 Further suggesting a modulating effect of dietary chloride on blood pressure, in hypertensive and normotensive subjects, substitution of dietary NaCl with equimolar sodium bicarbonate leads to a reduction of blood pressure.4,5 Additionally, in hypertensive humans, the reduction of blood pressure by dietary potassium is attenuated by potassium chloride compared with that of potassium citrate.6 Because the blood pressure increment in response …