ReviewPathogenesis of essential hypertension: historical paradigms and modern insightsJohnson, Richard Ja; Feig, Dan Ib; Nakagawa, Takahikoa; Sanchez-Lozada, L Gabrielac; Rodriguez-Iturbe, BernardodAuthor Information aDivision of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, Florida, USA bDivision of Pediatric Nephrology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA cInstituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico dHospital Universitario and Universidad del Zulia, Maracaibo, Venezuela Received 14 June, 2007 Revised 18 August, 2007 Accepted 25 September, 2007 Correspondence to Richard J. Johnson, MD, FACP, J. Robert Cade Professor of Nephrology, Department of Nephrology, Hypertension and Transplantation, University of Florida, Room CG98, PO Box 100224, 1600 SW Archer Road, Gainesville, FL 32610-0224, USA Tel: +1 352 392 4007; fax: +1 352 392 5465; e-mail: [email protected] Journal of Hypertension: March 2008 - Volume 26 - Issue 3 - p 381-391 doi: 10.1097/HJH.0b013e3282f29876 Buy Metrics Abstract 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.