Document Detail

Aldosterone does not contribute to renal p21 expression during the development of angiotensin II-induced hypertension in mice.
MedLine Citation:
PMID:  22113172     Owner:  NLM     Status:  MEDLINE    
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.
CONCLUSION: 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.
Daisuke Nakano; Bai Lei; Kento Kitada; Hirofumi Hitomi; Hiroyuki Kobori; Hirohito Mori; Kazushi Deguchi; Tsutomu Masaki; Tohru Minamino; Akira Nishiyama
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-11-24
Journal Detail:
Title:  American journal of hypertension     Volume:  25     ISSN:  1941-7225     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-15     Completed Date:  2012-06-12     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  United States    
Other Details:
Languages:  eng     Pagination:  354-8     Citation Subset:  IM    
Copyright Information:
© 2012 American Journal of Hypertension, Ltd.
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MeSH Terms
Actins / drug effects
Aldosterone / physiology*
Angiotensin II / pharmacology*
Antihypertensive Agents / pharmacology
Blood Pressure / drug effects*
Cell Aging / genetics*
Genes, p16 / drug effects
Genes, p53 / drug effects
Hydralazine / pharmacology
Hypertension / chemically induced,  genetics*
Imidazoles / pharmacology
Kidney / metabolism*
Mice, Inbred C57BL
Sirtuin 1 / drug effects,  genetics
Sodium Chloride / pharmacology
Spironolactone / analogs & derivatives,  pharmacology
Tetrazoles / pharmacology
p21-Activated Kinases / genetics*
Grant Support
Reg. No./Substance:
0/Actins; 0/Antihypertensive Agents; 0/Imidazoles; 0/Tetrazoles; 11128-99-7/Angiotensin II; 26NAK24LS8/Hydralazine; 27O7W4T232/Spironolactone; 4964P6T9RB/Aldosterone; 6995V82D0B/eplerenone; 7647-14-5/Sodium Chloride; 8W1IQP3U10/olmesartan; EC Kinases; EC 3.5.1.-/Sirt1 protein, mouse; EC 3.5.1.-/Sirtuin 1

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