Salt intake, endothelial dysfunction, and salt-sensitive hypertension

Abstract

Numerous epidemiologic and clinical studies have demonstrated a clear relationship between high salt intake and blood pressure. However, the mechanisms of a salt-induced increase in blood pressure--a phenomenon known as salt sensitivity--and the heterogeneity of this effect are far from being completely understood. Endothelial dysfunction, and especially the nitric oxide system, is implicated in both experimental and clinical hypertension. Animal studies indicate that endogenous nitric oxide plays an important role in renal hemodynamics and sodium homeostasis, inducing renal vasodilation and natriuresis. Studies of essential hypertensive patients have also suggested that both high salt intake and salt sensitivity are associated with impaired endothelial function. Although there are many hypotheses concerning the nature of salt sensitivity, clinical data indicate that salt-sensitive patients may be unable to up-regulate the production of nitric oxide in response to salt intake. This endothelial dysfunction, which is more frequent in salt-sensitive than in salt-resistant essential hypertensive patients, may partially explain the blood pressure increase in response to salt intake and may underlie the more pronounced target organ damage and cardiovascular risk in salt-sensitive patients.

Figure 1

Effects of NG‐monomethyl‐L‐arginine (L‐NMMA) on mean arterial pressure (MAP) in salt‐sensitive and salt‐resistant Dahl/Rapp rats (SS/DR and SR/DR) and Sprague‐Dawley rats (SD) during low and high salt intake ²⁸

Figure 2

Changes in plasma concentration and 24‐hour urinary excretion of endothelium‐derived products in salt‐sensitive and salt‐resistant essential hypertensive patients during low and high salt periods ⁹ _cGMP=cyclic guanosine monophosphate

Figure 3

Changes in forearm blood flow in response to increasing doses of acetylcholine (left), an endothelium‐dependent vasodilator, and sodium nitroprusside (right), an endothelium‐independent vasodilator, in 26 salt‐sensitive and 19 salt‐resistant hypertensive patients. Compared with salt‐resistant hypertensives, salt‐sensitive patients display a significant reduction in acetylcholine‐induced maximal vasodilation (p=0.005 comparing dose‐response curves between groups). Adapted with permission from Hypertension. 2001;37 :444–448. ⁹

Figure 4

Changes in forearm blood flow in response to acetylcholine in the presence and absence of N^G‐monomethyl‐L‐arginine (L‐NMMA) (a nitric oxide synthase inhibitor), in salt‐resistant (left) and salt‐sensitive (right) essential hypertensive patients. The L‐NMMA infusion decreased both baseline forearm blood flow and maximal acetylcholine‐induced vasodilation. This latter effect was significantly more pronounced in salt‐resistant, compared to salt‐sensitive subjects. Adapted with permission from Hypertension. 2001;37: 444–448. ⁹