Document Detail


Renal proximal tubule angiotensin AT1A receptors regulate blood pressure.
MedLine Citation:
PMID:  21753145     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
All components of the renin angiotensin system necessary for ANG II generation and action have been reported to be present in renal proximal convoluted tubules. Given the close relationship between renal sodium handling and blood pressure regulation, we hypothesized that modulating the action of ANG II specifically in the renal proximal tubules would alter the chronic level of blood pressure. To test this, we used a proximal tubule-specific, androgen-dependent, promoter construct (KAP2) to generate mice with either overexpression of a constitutively active angiotensin type 1A receptor transgene or depletion of endogenous angiotensin type 1A receptors. Androgen administration to female transgenic mice caused a robust induction of the transgene in the kidney and increased baseline blood pressure. In the receptor-depleted mice, androgen administration to females resulted in a Cre recombinase-mediated deletion of angiotensin type 1A receptors in the proximal tubule and reduced blood pressure. In contrast to the changes observed at baseline, there was no difference in the blood pressure response to a pressor dose of ANG II in either experimental model. These data, from two separate mouse models, provide evidence that ANG II signaling via the type 1A receptor in the renal proximal tubule is a regulator of systemic blood pressure under baseline conditions.
Authors:
Huiping Li; Eric T Weatherford; Deborah R Davis; Henry L Keen; Justin L Grobe; Alan Daugherty; Lisa A Cassis; Andrew M Allen; Curt D Sigmund
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-13
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  301     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-07     Completed Date:  2011-12-06     Revised Date:  2012-05-01    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1067-77     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
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MeSH Terms
Descriptor/Qualifier:
Androgens / pharmacology
Angiotensin II / pharmacology
Animals
Blood Pressure / drug effects,  physiology*
Female
Integrases / metabolism
Kidney Tubules, Proximal / metabolism*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Models, Animal
Receptor, Angiotensin, Type 1 / drug effects,  genetics,  metabolism*
Signal Transduction / drug effects,  physiology
Grant Support
ID/Acronym/Agency:
HL-048058/HL/NHLBI NIH HHS; HL-061446/HL/NHLBI NIH HHS; HL-062846/HL/NHLBI NIH HHS; HL-073085/HL/NHLBI NIH HHS; HL-080100/HL/NHLBI NIH HHS; HL-084207/HL/NHLBI NIH HHS; K99/R00 HL-098276/HL/NHLBI NIH HHS; R01 HL061446/HL/NHLBI NIH HHS; R01 HL073085-08/HL/NHLBI NIH HHS; R01 HL073085-09/HL/NHLBI NIH HHS; R37 HL048058-19/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Androgens; 0/Receptor, Angiotensin, Type 1; 11128-99-7/Angiotensin II; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases

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


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