Document Detail


The complex interplay between cyclooxygenase-2 and angiotensin II in regulating kidney function.
MedLine Citation:
PMID:  22080858     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: Cyclooxygenase-2 (COX-2) plays a critical role in modulating deleterious actions of angiotensin II (Ang II) where there is an inappropriate activation of the renin-angiotensin system (RAS). This review discusses the recent developments regarding the complex interactions by which COX-2 modulates the impact of an activated RAS on kidney function and blood pressure.
RECENT FINDINGS: Normal rats with increased COX-2 activity but with different intrarenal Ang II activity because of sodium restriction or chronic treatment with angiotensin-converting enzyme (ACE) inhibitors showed similar renal hemodynamic responses to COX-2-selective inhibition (nimesulide) indicating independence from the intrarenal Ang II activity. COX-2-dependent maintenance of medullary blood flow was consistent and not dependent on dietary salt or ACE inhibition. In contrast, COX-2 influences on sodium excretion were contingent on the prevailing RAS activity. In chronic hypertensive models, COX-2 inhibition elicited similar reductions in kidney function, but COX-2 metabolites contribute to rather than ameliorate the hypertension.
SUMMARY: The maintenance of renal hemodynamics reflects direct and opposing effects of Ang II and COX-2 metabolites. The antagonism in water and electrolyte reabsorption is dependent on the prevailing intrarenal Ang II activity. The recent functional experiments demonstrate a beneficial modulation of Ang II by COX-2 except in the presence of inflammation promoted by hypertension, hyperglycemia, and oxidative stress.
Authors:
Torrance Green; Alexis A Gonzalez; Kenneth D Mitchell; L Gabriel Navar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Current opinion in nephrology and hypertension     Volume:  21     ISSN:  1473-6543     ISO Abbreviation:  Curr. Opin. Nephrol. Hypertens.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-07     Completed Date:  2012-04-10     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  9303753     Medline TA:  Curr Opin Nephrol Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  7-14     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / metabolism*
Animals
Antihypertensive Agents / therapeutic use
Blood Pressure
Cyclooxygenase 2 / metabolism*
Cyclooxygenase 2 Inhibitors / therapeutic use
Humans
Hypertension / drug therapy,  enzymology*,  etiology,  physiopathology
Kidney / drug effects,  enzymology*,  physiopathology
Kidney Diseases / complications,  drug therapy,  enzymology*,  physiopathology
Renin-Angiotensin System* / drug effects
Signal Transduction
Grant Support
ID/Acronym/Agency:
HL-18426/HL/NHLBI NIH HHS; HL-26371/HL/NHLBI NIH HHS; P20 RR-017659/RR/NCRR NIH HHS; P20 RR017659/RR/NCRR NIH HHS; P20 RR017659-09/RR/NCRR NIH HHS; R01 HL018426/HL/NHLBI NIH HHS; R01 HL018426-31S1/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Cyclooxygenase 2 Inhibitors; 11128-99-7/Angiotensin II; EC 1.14.99.1/Cyclooxygenase 2
Comments/Corrections

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