Pathogenesis of essential hypertension: Historical paradigms and modern insights

Academic Article


  • Since its first identification in the late 1800s, a variety of etiologies for essential hypertension have been proposed. In this paper we review the primary proposed hypotheses in the context of both the time in which they were proposed as well as the subsequent studies performed over the years. From these various insights, we propose a current paradigm to explain the renal mechanisms underlying the hypertension epidemic today. Specifically, we propose that hypertension is initiated by agents that cause systemic and intrarenal vasoconstriction. Over time intrarenal injury develops with microvascular disease, interstitial T cell and macrophage recruitment with the induction of an autoimmune response, with local angiotensin II formation and oxidant generation. These changes maintain intrarenal vasoconstriction and hypoxia with a change in local vasoconstrictor-vasodilator balance favoring sodium retention. Both genetic and congenital (nephron number) mechanisms have profound influence on this pathway. As blood pressure rises, renal ischemia is ameliorated and sodium balance restored completely (in salt-resistant) or partially (in salt-sensitive) hypertension, but at the expense of a rightward shift in the pressure natriuresis curve and persistent hypertension. © 2008 Lippincott Williams & Wilkins, Inc.
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    Published In

    Digital Object Identifier (doi)

    Author List

  • Johnson RJ; Feig DI; Nakagawa T; Sanchez-Lozada LG; Rodriguez-Iturbe B
  • Start Page

  • 381
  • End Page

  • 391
  • Volume

  • 26
  • Issue

  • 3