Document Detail


The arterial depressor response to chronic low-dose angiotensin II infusion in female rats is estrogen dependent.
MedLine Citation:
PMID:  22031787     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The complex role of the renin-angiotensin-system (RAS) in arterial pressure regulation has been well documented. Recently, we demonstrated that chronic low-dose angiotensin II (ANG II) infusion decreases arterial pressure in female rats via an AT(2)R-mediated mechanism. Estrogen can differentially regulate components of the RAS and is known to influence arterial pressure regulation. We hypothesized that AT(2)R-mediated depressor effects evident in females were estrogen dependent and thus would be abolished by ovariectomy and restored by estrogen replacement. Female Sprague-Dawley rats underwent ovariectomy or sham surgery and were treated with 17β-estradiol or placebo. Mean arterial pressure (MAP) was measured via telemetry in response to a 2-wk infusion of ANG II (50 ng·kg(-1)·min(-1) sc) or saline. MAP significantly decreased in females treated with ANG II (-10 ± 2 mmHg), a response that was abolished by ovariectomy (+4 ± 2 mmHg) and restored with estrogen replacement (-6 ± 2 mmHg). Cardiac and renal gene expression of components of the RAS was differentially regulated by estrogen, such that overall, estrogen shifted the balance of the RAS toward the vasodilatory axis. In conclusion, estrogen-dependent mechanisms offset the vasopressor actions of ANG II by enhancing RAS vasodilator pathways in females. This highlights the potential for these vasodilator pathways as therapeutic targets, particularly in women.
Authors:
Amanda K Sampson; Lucinda M Hilliard; Karen M Moritz; Merlin C Thomas; Chris Tikellis; Robert E Widdop; Kate M Denton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-10-26
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  302     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-26     Completed Date:  2012-03-26     Revised Date:  2012-05-23    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R159-65     Citation Subset:  IM    
Affiliation:
Department of Physiology, Monash University, Clayton, Victoria, Australia. Amanda.sampson@bakeridi.edu.au
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MeSH Terms
Descriptor/Qualifier:
Angiotensin I / blood
Angiotensin II / administration & dosage,  pharmacology*
Animals
Blood Pressure / drug effects*,  physiology*
Dose-Response Relationship, Drug
Estradiol / pharmacology
Estrogens / deficiency,  physiology*
Female
Infusions, Subcutaneous
Kidney / metabolism
Models, Animal
Ovariectomy*
Peptide Fragments / blood
Peptidyl-Dipeptidase A / metabolism
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 2 / metabolism
Renin-Angiotensin System / drug effects,  physiology
Signal Transduction / drug effects,  physiology
Vasoconstrictor Agents / administration & dosage,  pharmacology*
Chemical
Reg. No./Substance:
0/Estrogens; 0/Peptide Fragments; 0/Receptor, Angiotensin, Type 2; 0/Vasoconstrictor Agents; 0/angiotensin I (1-7); 11128-99-7/Angiotensin II; 50-28-2/Estradiol; 9041-90-1/Angiotensin I; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.17.-/angiotensin converting enzyme 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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