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Regional Variation in Aortic AT1b Receptor mRNA Abundance Is Associated with Contractility but Unrelated to Atherosclerosis and Aortic Aneurysms

BACKGROUND: Angiotensin II (AngII), the main bioactive peptide of the renin angiotensin system, exerts most of its biological actions through stimulation of AngII type 1 (AT1) receptors. This receptor is expressed as 2 structurally similar subtypes in rodents, termed AT1a and AT1b. Although AT1a rec...

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Autores principales: Poduri, Aruna, Owens, A. Phillip, Howatt, Deborah A., Moorleghen, Jessica J., Balakrishnan, Anju, Cassis, Lisa A., Daugherty, Alan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485205/
https://www.ncbi.nlm.nih.gov/pubmed/23119030
http://dx.doi.org/10.1371/journal.pone.0048462
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author Poduri, Aruna
Owens, A. Phillip
Howatt, Deborah A.
Moorleghen, Jessica J.
Balakrishnan, Anju
Cassis, Lisa A.
Daugherty, Alan
author_facet Poduri, Aruna
Owens, A. Phillip
Howatt, Deborah A.
Moorleghen, Jessica J.
Balakrishnan, Anju
Cassis, Lisa A.
Daugherty, Alan
author_sort Poduri, Aruna
collection PubMed
description BACKGROUND: Angiotensin II (AngII), the main bioactive peptide of the renin angiotensin system, exerts most of its biological actions through stimulation of AngII type 1 (AT1) receptors. This receptor is expressed as 2 structurally similar subtypes in rodents, termed AT1a and AT1b. Although AT1a receptors have been studied comprehensively, roles of AT1b receptors in the aorta have not been defined. METHODOLOGY/RESULTS: We initially compared the regional distribution of AT1b receptor mRNA with AT1a receptor mRNA in the aorta. mRNA abundance of both subtypes increased from the proximal to the distal aorta, with the greatest abundance in the infra-renal region. Corresponding to the high mRNA abundance for both receptors, only aortic rings from the infra-renal aorta contracted in response to AngII stimulation. Despite the presence of both receptor transcripts, deletion of AT1b receptors, but not AT1a receptors, diminished AngII-induced contractility. To determine whether absence of AT1b receptors influenced aortic pathologies, we bred AT1b receptor deficient mice into an LDL receptor deficient background. Mice were fed a diet enriched in saturated fat and infused with AngII (1,000 ng/kg/min). Parameters that could influence development of aortic pathologies, including systolic blood pressure and plasma cholesterol concentrations, were not impacted by AT1b receptor deficiency. Absence of AT1b receptors also had no effect on size of aortic atherosclerotic lesions and aortic aneurysms in both the ascending and abdominal regions. CONCLUSIONS/SIGNIFICANCE: Regional abundance of AT1b receptor mRNA coincided with AngII-induced regional contractility, but it was not associated with AngII-induced aortic pathologies.
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spelling pubmed-34852052012-11-01 Regional Variation in Aortic AT1b Receptor mRNA Abundance Is Associated with Contractility but Unrelated to Atherosclerosis and Aortic Aneurysms Poduri, Aruna Owens, A. Phillip Howatt, Deborah A. Moorleghen, Jessica J. Balakrishnan, Anju Cassis, Lisa A. Daugherty, Alan PLoS One Research Article BACKGROUND: Angiotensin II (AngII), the main bioactive peptide of the renin angiotensin system, exerts most of its biological actions through stimulation of AngII type 1 (AT1) receptors. This receptor is expressed as 2 structurally similar subtypes in rodents, termed AT1a and AT1b. Although AT1a receptors have been studied comprehensively, roles of AT1b receptors in the aorta have not been defined. METHODOLOGY/RESULTS: We initially compared the regional distribution of AT1b receptor mRNA with AT1a receptor mRNA in the aorta. mRNA abundance of both subtypes increased from the proximal to the distal aorta, with the greatest abundance in the infra-renal region. Corresponding to the high mRNA abundance for both receptors, only aortic rings from the infra-renal aorta contracted in response to AngII stimulation. Despite the presence of both receptor transcripts, deletion of AT1b receptors, but not AT1a receptors, diminished AngII-induced contractility. To determine whether absence of AT1b receptors influenced aortic pathologies, we bred AT1b receptor deficient mice into an LDL receptor deficient background. Mice were fed a diet enriched in saturated fat and infused with AngII (1,000 ng/kg/min). Parameters that could influence development of aortic pathologies, including systolic blood pressure and plasma cholesterol concentrations, were not impacted by AT1b receptor deficiency. Absence of AT1b receptors also had no effect on size of aortic atherosclerotic lesions and aortic aneurysms in both the ascending and abdominal regions. CONCLUSIONS/SIGNIFICANCE: Regional abundance of AT1b receptor mRNA coincided with AngII-induced regional contractility, but it was not associated with AngII-induced aortic pathologies. Public Library of Science 2012-10-31 /pmc/articles/PMC3485205/ /pubmed/23119030 http://dx.doi.org/10.1371/journal.pone.0048462 Text en © 2012 Poduri et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Poduri, Aruna
Owens, A. Phillip
Howatt, Deborah A.
Moorleghen, Jessica J.
Balakrishnan, Anju
Cassis, Lisa A.
Daugherty, Alan
Regional Variation in Aortic AT1b Receptor mRNA Abundance Is Associated with Contractility but Unrelated to Atherosclerosis and Aortic Aneurysms
title Regional Variation in Aortic AT1b Receptor mRNA Abundance Is Associated with Contractility but Unrelated to Atherosclerosis and Aortic Aneurysms
title_full Regional Variation in Aortic AT1b Receptor mRNA Abundance Is Associated with Contractility but Unrelated to Atherosclerosis and Aortic Aneurysms
title_fullStr Regional Variation in Aortic AT1b Receptor mRNA Abundance Is Associated with Contractility but Unrelated to Atherosclerosis and Aortic Aneurysms
title_full_unstemmed Regional Variation in Aortic AT1b Receptor mRNA Abundance Is Associated with Contractility but Unrelated to Atherosclerosis and Aortic Aneurysms
title_short Regional Variation in Aortic AT1b Receptor mRNA Abundance Is Associated with Contractility but Unrelated to Atherosclerosis and Aortic Aneurysms
title_sort regional variation in aortic at1b receptor mrna abundance is associated with contractility but unrelated to atherosclerosis and aortic aneurysms
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485205/
https://www.ncbi.nlm.nih.gov/pubmed/23119030
http://dx.doi.org/10.1371/journal.pone.0048462
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