title: Sympathetic overactivity as a cause of hypertension in chronic renal failure.
abstract: OBJECTIVE
  To review the current literature on sympathetic mediation of hypertension in chronic renal failure.
  
  
  BACKGROUND
  Hypertension is present in the vast majority of patients with chronic renal failure and constitutes a major risk factor for the excessive cardiovascular morbidity and mortality in this patient population. Although, traditionally, this hypertension is thought to be largely volume-dependent, an increasing body of literature suggests that there is an important sympathetic neural component. Microneurographic studies have demonstrated sympathetic overactivity without baroreflex impairment in both hypertensive chronic hemodialysis patients as well as in those with less advanced renal insufficiency. Sympathetic nerve activity was found to be normal in hemodialysis patients with bilateral nephrectomy, leading to the hypothesis that sympathetic overactivity in uremia is caused by a neurogenic signal (carried by renal afferents) arising in the failing kidney. This hypothesis is supported by rat studies showing that renal deafferentation abrogates hypertension in the 5/6 nephrectomy model of chronic renal insufficiency. In addition, in patients with chronic renal insufficiency and renin-dependent hypertension, sympathetic overactivity was normalized by chronic angiotensin converting enzyme inhibition but not by calcium channel blockade, implicating a major central neural action of angiotensin II.
  
  
  CONCLUSIONS
  Sympathetic overactivity in chronic renal failure is caused by neurohormonal mechanisms arising in the failing kidney. Future clinical studies are needed to determine whether normalization of sympathetic activity should constitute an important therapeutic goal in this high-risk patient population.
authors.affiliation: Department of Internal Medicine, Division of Hypertension, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8586, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Augustyniak
authors.forename: Meryem
authors.initials: M
authors.lastname: Tuncel
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhang
authors.forename: Robert D
authors.initials: RD
authors.lastname: Toto
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Victor
mesh_terms: D000818:Animals; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000503:physiopathology*; D051381:Rats; D013564:Sympathetic Nervous System / Q000503:physiopathology*