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A knockout approach indicates a minor vasoconstrictor role for vascular _1B-adrenoceptors in mouse

Institute of Biomedical and Life Sciences, Division of Neuroscience and Biomedical Systems, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland

Pharmacological analysis alone has failed to clarify the role of the three ₁-adrenoceptor subtypes in modulating vascular tone, due to a lack of sufficiently selective antagonists, particularly for the _1B-adrenoceptor, and the complexity when three receptor subtypes are potentially activated by the same agonist. We adopted a combined genetics/ pharmacology strategy based on the _1B-adrenoceptor knockout (KO) mouse. The potency of three ₁-adrenoceptor antagonists vs. phenylephrine was tested in aorta, carotid, mesenteric, and caudal isolated arteries from KO and wild-type (WT) mice. In the KO mouse the pharmacology became straightforward, showing _1D in two major conducting arteries (aorta and carotid) and _1A in two distributing arteries (mesenteric and caudal). By combining antagonist pharmacology and genetics, we provide a simplified analysis of ₁-mediated vasoconstriction, demonstrating that _1D and _1A are the major subtypes involved in vasoconstriction, with a minor but definite contribution from _1B in every vessel.

₁-adrenoceptors; mouse aorta; arteries; functional genomics

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