Two alpha1-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation.

Détails

ID Serval
serval:BIB_369FAE144856
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Two alpha1-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation.
Périodique
Molecular Pharmacology
Auteur(s)
Hosoda C., Koshimizu T.A., Tanoue A., Nasa Y., Oikawa R., Tomabechi T., Fukuda S., Shinoura H., Oshikawa S., Takeo S., Kitamura T., Cotecchia S., Tsujimoto G.
ISSN
0026-895X (Print)
ISSN-L
0026-895X
Statut éditorial
Publié
Date de publication
2005
Volume
67
Numéro
3
Pages
912-922
Langue
anglais
Résumé
To study the functional role of individual alpha1-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the alpha1B-AR and/or alpha1D-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the alpha1D-AR knockout and alpha1B-/alpha1D-AR double knockout mice, but not the alpha1B-AR knockout mice, had significantly (p < 0.05) lower levels of basal systolic and mean arterial BP than wild-type mice in nonanesthetized condition, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. All mutants showed a significantly (p < 0.05) reduced catecholamine-induced pressor and vasoconstriction responses. It is noteworthy that the infusion of norepinephrine did not elicit any pressor response at all in alpha1B-/alpha1D-AR double knockout mice. In an attempt to further examine alpha1-AR subtype, which is involved in the genesis or maintenance of hypertension, BP after salt loading was monitored by tail-cuff readings and confirmed at the endpoint by direct intra-arterial recording. After salt loading, alpha1B-AR knockout mice developed a comparable level of hypertension to wild-type mice, whereas mice lacking alpha1D-AR had significantly (p < 0.05) attenuated BP and lower levels of circulating catecholamines. Our data indicated that alpha1B- and alpha1D-AR subtypes participate cooperatively in BP regulation; however, the deletion of the functional alpha1D-AR, not alpha1B-AR, leads to an antihypertensive effect. The study shows differential contributions of alpha1B- and alpha1D-ARs in BP regulation.
Mots-clé
Animals, Aorta, Thoracic/drug effects, Aorta, Thoracic/physiology, Blood Pressure/drug effects, Blood Pressure/physiology, Cloning, Molecular, Heart Rate/drug effects, Heart Rate/physiology, Mice, Mice, Knockout, Potassium Chloride/pharmacology, Prazosin/pharmacokinetics, Radioligand Assay, Receptors, Adrenergic, alpha-1/deficiency, Receptors, Adrenergic, alpha-1/drug effects, Recombinant Proteins/drug effects, Recombinant Proteins/metabolism, Vasoconstriction/drug effects, Vasoconstriction/physiology
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 13:24
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