UCSF

Prevailing theory holds that abnormally large increases in renal salt retention and cardiac output are early pathophysiologic events mediating initiation of most instances of salt-induced hypertension. This theory has come under increasing scrutiny because it is based on studies that lack measurements of sodium balance and cardiac output obtained during initiation of salt-loading in proper normal controls, i.e., salt-resistant subjects with normal blood pressure. Here we make the case for a “vasodysfunction” theory for initiation of salt-induced hypertension: In response to an increase in salt intake, a subnormal decrease in total peripheral resistance that involves a subnormal decrease in renal vascular resistance, in the absence of abnormally large increases in sodium retention and cardiac output, is the hemodynamic abnormality that usually mediates initiation of salt-induced increases in blood pressure (BP). It is the failure to normally decrease vascular resistance in response to salt loading that enables a normal increase of cardiac output to initiate the salt-induced increase in blood pressure. This theory is based on the results of properly controlled studies which consistently demonstrate that in salt-sensitive subjects, salt-loading initiates increased BP through a hemodynamic mechanism that: 1) does not usually involve early increases in sodium retention and cardiac output greater than those which occur with salt-loading in normal controls, and 2) usually involves an early failure to decrease vascular resistance to the same extent as that observed during salt-loading in normal controls. Multiple mechanisms including disturbances in nitric oxide and sympathetic nervous system activity likely underlie this subnormal vasodilatory response to salt that usually precedes and initiates salt-induced hypertension.