Volume 2, Issue 1 (Feb 2014)
Res Mol Med (RMM) 2014, 2(1): 26-34 |
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Malekzadeh Shafaroudi M, Dlay C J. Endothelial Vasodilator Angiotensin Receptors are Changing in Mice with Ageing. Res Mol Med (RMM) 2014; 2 (1) :26-34
URL: http://rmm.mazums.ac.ir/article-1-59-en.html
URL: http://rmm.mazums.ac.ir/article-1-59-en.html
1- Department of Anatomy, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran , malek1344@gmail.com
2- Autonomic Physiology Unit, Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, Scotland
2- Autonomic Physiology Unit, Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, Scotland
Abstract: (25000 Views)
Background: The vascular function of Angiotensin II-type-2 receptors in adults is controversial. We sought their location and function in mouse aortic rings at young and old mice.
Materials and Methods: Male C57Bl mice (aged 4 and 14 months) were killed by CO2. The descending thoracic aorta was cleaned and dissected into rings. Aortic rings were mounted in Krebs’ solution at 37 °C and then setup in a multi-myograph. Also segments of aorta were incubated with or without antagonists then TMR-Angiotensin II and/or QAPB were added.
Results: At 4 months, angiotensin II, at low concentrations, caused losartan-sensitive contraction higher concentrations (100nmol/L) caused relaxation sensitive to endothelial denudation, L-NAME or PD123319. Angiotensin II-type-1 receptors blockade plus L-NAME revealed PD123319-sensitive contraction. At old mice, aortic relaxation to angiotensin II was lost. At young mice, Losartan and PD123319, together but not separately, abolished binding of fluorescent TMR-angiotensin II, to endothelium and smooth muscle, indicatin Angiotensin II-type-1 and Angiotensin II-type-2 receptors in both cell types. In contrast, at 14 months endothelial fluorescence was eliminated by losartan.
Conclusion: Aortic endothelium of young adult mice has Angiotensin II-type-2 receptors that release vasodilator nitric oxide. This is lost in old age, explaining age-related loss of vasodilatation by Angiotensin II. Aortic smooth muscle has pro-contractile Angiotensin II-type-1 and Angiotensin II-type-2 receptors in young and old mice. Reciprocal actions of angiotensin II are, due to Angiotensin II-type-1 and Angiotensin II-type-2 receptors situated on different cell types but only at young ages, Angiotensin II-type-1 receptors of unknown function are present on endothelium.
Conclusion: Aortic endothelium of young adult mice has Angiotensin II-type-2 receptors that release vasodilator nitric oxide. This is lost in old age, explaining age-related loss of vasodilatation by Angiotensin II. Aortic smooth muscle has pro-contractile Angiotensin II-type-1 and Angiotensin II-type-2 receptors in young and old mice. Reciprocal actions of angiotensin II are, due to Angiotensin II-type-1 and Angiotensin II-type-2 receptors situated on different cell types but only at young ages, Angiotensin II-type-1 receptors of unknown function are present on endothelium.
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