Title:Salt-Sensitive Hypertension: Perspectives on Intrarenal Mechanisms
Volume: 11
Issue: 1
Author(s): Dewan S.A. Majid, Minolfa C. Prieto and Luis Gabriel Navar
Affiliation:
Keywords:
Angiotensin II, angiotensinogen, inflammatory cytokines, intrarenal renin-angiotensin system, oxidative stress,
peroxynitrite, tumor necrosis factor-alpha.
Abstract: Salt sensitive hypertension is characterized by increases in blood pressure in response to
increases in dietary salt intake and is associated with an enhanced risk of cardiovascular and renal
morbidity. Although researchers have sought for decades to understand how salt sensitivity develops
in humans, the mechanisms responsible for the increases in blood pressure in response to high salt
intake are complex and only partially understood. Until now, scientists have been unable to explain
why some individuals are salt sensitive and others are salt resistant. Although a central role for the
kidneys in the development of salt sensitivity and hypertension has been generally accepted, it is also
recognized that hypertension is of multifactorial origin and a variety of factors can induce, or prevent, blood pressure
responsiveness to the manipulation of salt intake. Excess salt intake in susceptible persons may also induce inappropriate
central and sympathetic nervous system responses and increase the production of intrarenal angiotensin II, catecholamines
and other factors such as oxidative stress and inflammatory cytokines. One key factor is the concomitant inappropriate or
paradoxical activation of the intrarenal renin-angiotensin system, by high salt intake. This is reflected by the increases in
urinary angiotensinogen during high salt intake in salt sensitive models. A complex interaction between neuroendocrine
factors and the kidney may underlie the propensity for some individuals to retain salt and develop salt-dependent
hypertension. In this review, we focus mainly on the renal contributions that provide the mechanistic links between
chronic salt intake and the development of hypertension.
