According to prevailing theory, salt-sensitive subjects have an impaired renal ability to excrete a salt load that usually causes them to retain more sodium than normal salt-resistant subjects. 8, 10, 12–16 The retention of abnormally large amounts of salt and water is held to cause abnormally large increases in sodium balance, blood volume, and a transient, abnormally large increase in cardiac output that contributes importantly to the hemodynamic initiation of increased blood pressure. 8, 11, 12 Many investigators also note a role for abnormalities in the control of systemic vascular resistance in the hemodynamic initiation of salt-induced increases in blood pressure; that is, they do not contend that only an abnormally large increase in cardiac output induced by abnormally large increases in renal retention of sodium and water is responsible for the hemodynamic initiation of salt-induced increases in blood pressure. 15, 18–24

It should be noted that views holding that abnormal levels of both cardiac output and systemic vascular resistance contribute to the hemodynamic initiation of salt-induced hypertension differ from the view championed by Lifton et al8 and others. 11, 12, 25–27 This view shown in Figure 1 holds that during the initiation of salt-induced hypertension, systemic vascular resistance is “normal” and pathogenically uninvolved in the initial pressor effect of salt. Abnormal systemic vascular resistance is held to be secondary only to increases in cardiac output and blood pressure caused by abnormal increases in renal retention of salt and water (Figure 1). This volume-loading theory (Figure 1), sometimes referred to as the autoregulation theory, 28 also describes the sequence of events through which the phenomenon of abnormal pressure natriuresis is said to initiate and sustain salt-induced hypertension. 29–32 Most theories of salt-induced hypertension share 2 core tenets:(1) Salt-sensitive subjects have a subnormal ability to excrete a salt load that causes them to retain more sodium than normal salt-resistant subjects, and (2) such an abnormally increased renal retention of sodium causes an abnormally large increase in cardiac output and thereby contributes importantly to the hemodynamic initiation of saltinduced increases in blood pressure. Here, we challenge the validity of both these tenets.