title: Aldosterone does not contribute to renal p21 expression during the development of angiotensin II-induced hypertension in mice.
abstract: BACKGROUND
  We recently reported that aldosterone-induced cellular senescence via an increase in p21, a cyclin-dependent kinase (CDK) inhibitor, in rat kidney and cultured human proximal tubular cells. In the present study, we investigated the contribution of aldosterone to the renal p21 expression and senescence during the development of angiotensin II (AngII)-induced hypertension.
  
  
  METHODS
  Mice received 1% salt in drinking water and vehicle or AngII, and were divided into five groups: 1, vehicle; 2, AngII; 3, AngII+olmesartan; 4, AngII+eplerenone; and 5, AngII+hydralazine.
  
  
  RESULTS
  Plasma aldosterone levels were increased by AngII infusion. Eplerenone further elevated the plasma aldosterone level, but olmesartan and hydralazine did not. AngII group showed significant increase in blood pressure compared to vehicle. Olmesartan and hydralazine, but not eplerenone, suppressed the AngII-salt hypertension. The increase in urinary protein excretion by AngII-salt was suppressed only by olmesartan. AngII with high salt induced a greater expression of p21 mRNA in the kidney than vehicle. Olmesartan abolished the increase in p21 expression, whereas neither eplerenone nor hydralazine affected it. AngII with high salt did not change the expression of p16, another CDK inhibitor. The mice lacking p21 showed identical changes on blood pressure and albuminuria in response to AngII with high salt compared to wild type.
  
  
  CONCLUSIONS
  These results suggest that aldosterone does not predominantly contribute to renal p21 expression and senescence during the development of AngII-salt hypertension, and that the increase in p21 in the kidney is not likely involved in the development of hypertension and albuminuria.
authors: Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan. dnakano@med.kagawa-u.ac.jp
authors: Daisuke
authors: D
authors: Nakano
authors: Bai
authors: B
authors: Lei
authors: Kento
authors: K
authors: Kitada
authors: Hirofumi
authors: H
authors: Hitomi
authors: Hiroyuki
authors: H
authors: Kobori
authors: Hirohito
authors: H
authors: Mori
authors: Kazushi
authors: K
authors: Deguchi
authors: Tsutomu
authors: T
authors: Masaki
authors: Tohru
authors: T
authors: Minamino
authors: Akira
authors: A
authors: Nishiyama
mesh_terms: D000199:Actins / Q000187:drug effects; D000450:Aldosterone / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D016922:Cellular Senescence / Q000235:genetics*; D000077545:Eplerenone; D019942:Genes, p16 / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics*; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D056564:Sirtuin 1 / Q000187:drug effects / Q000235:genetics; D012965:Sodium Chloride / Q000494:pharmacology; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D054462:p21-Activated Kinases / Q000235:genetics*
chemical_list: D000199:Actins; D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D006830:Hydralazine; D013148:Spironolactone; D012965:Sodium Chloride; D000450:Aldosterone; D000077545:Eplerenone; C437965:olmesartan; D054462:p21-Activated Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1