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Updated: Aug 18, 2026
Measurement of Endothelium-Dependent Vasorelaxation in the Mouse Thoracic Aorta Using Tensometric Small Volume Chamber Myography
Published on: August 12, 2022
Two "knockout" mouse models demonstrate that aortic vasodilatation is mediated via alpha2a-adrenoceptors located on
Majid Malekzadeh Shafaroudi1, Melissa McBride, Clare Deighan
1Autonomic Physiology Unit, Institute of Biomedical and Life Sciences, West Medical Bldg., University of Glasgow, Glasgow G12 8QQ, Scotland, UK.
Abstract:
UK-14,304 [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine]-mediated vasodilator responses were studied on wire myograph-mounted mouse aorta to determine the cells involved, mechanisms of action, and subtypes of alpha(2)-adrenoceptors. In the presence of induced tone, UK-14,304 produced concentration-related vasodilatation that was abolished by rauwolscine, N(omega)-nitro-L-arginine methyl ester (L-NAME), or endothelium removal, indicating that endothelial alpha(2)-adrenoceptors can release nitric oxide. In the alpha(2A)-adrenoceptor knockout mouse and the D79N mouse, a functional knockout of the alpha(2A)-adrenoceptor, these relaxant effects of UK-14,304 were lost, indicating the involvement of the alpha(2A)-adrenoceptor. UK-14,304 could also contract aorta: a small contraction occurred at high concentrations, was enhanced by L-NAME, and was absent in the alpha(1D)-adrenoceptor knockout mouse, indicating activation of the alpha(1D)-adrenoceptor. There was no evidence for a contractile alpha(2)-adrenoceptor-mediated response. A fluorescent ligand, quinazoline piperazine bodipy, antagonized the relaxant action of UK-14,304. This compound could be visualized on aortic endothelial cells, and its binding could be prevented by rauwolscine, providing direct evidence for the presence of alpha(2)-adrenoceptors on the endothelium. Norepinephrine reduced tone in the alpha(1D)-adrenoceptor knockout and controls, an effect blocked by rauwolscine and L-NAME but not by prazosin. This suggests that norepinephrine activates endothelial alpha(2)-adrenoceptors. In conclusion, the endothelium of mouse aorta has an alpha(2A)-adrenoceptor that responds to norepinephrine; promotes the release of nitric oxide, causing smooth muscle relaxation; and that can be directly visualized. Knockout or genetic malfunction of this receptor should increase arterial stiffness, exacerbated by raised catecholamines, and contribute to heart failure.
