A knockout approach indicates a minor vasoconstrictor role for vascular alpha1B-adrenoceptors in mouse.
Pharmacological analysis alone has failed to clarify the role of the three alpha(1)-adrenoceptor subtypes in modulating vascular tone, due to a lack of sufficiently selective antagonists, particularly for the alpha (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 alpha(1B)-adrenoceptor knockout (KO) mouse. The potency of three alpha(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 alpha(1D) in two major conducting arteries (aorta and carotid) and alpha(1A) in two distributing arteries (mesenteric and caudal). By combining antagonist pharmacology and genetics, we provide a simplified analysis of alpha(1)-mediated vasoconstriction, demonstrating that alpha(1D) and alpha(1A) are the major subtypes involved in vasoconstriction, with a minor but definite contribution from alpha(1B) in every vessel.
Daly
Craig J
CJ
Institute of Biomedical and Life Sciences, Division of Neuroscience and Biomedical Systems, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland. c.daly@bio.gla.ac.uk
Deighan
Clare
C
McGee
Ann
A
Mennie
Dawson
D
Ali
Zeeshan
Z
McBride
Melissa
M
McGrath
John C
JC
D058671:Adrenergic beta-1 Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D002339:Carotid Arteries / Q000502:physiology; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010656:Phenylephrine / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D058671:Adrenergic beta-1 Receptor Antagonists; D018342:Receptors, Adrenergic, beta-1; D014662:Vasoconstrictor Agents; D010656:Phenylephrine