regional variation in aortic at1b receptor mrna abundance is associated with contractility but unrelated to atherosclerosis and aortic aneurysms区域性主动脉at1b受体信使rna丰度的变化与收缩性但不相关的动脉粥样硬化和主动脉瘤.pdfVIP

Regional Variation in Aortic AT1b Receptor mRNA Abundance Is Associated with Contractility but Unrelated to Atherosclerosis and Aortic Aneurysms 1 1 1 1 1 Aruna Poduri , A. Phillip Owens, III , Deborah A. Howatt , Jessica J. Moorleghen , Anju Balakrishnan , Lisa A. Cassis2, Alan Daugherty1,3* 1 Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky, United States of America, 2 Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, Kentucky, United States of America, 3 Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky, United States of America Abstract 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 backgrou