Decreased blood pressure response in mice deficient of the alpha1b-adrenergic receptor.

Détails

ID Serval
serval:BIB_CDD89ECC9EAB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Decreased blood pressure response in mice deficient of the alpha1b-adrenergic receptor.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Cavalli A., Lattion A.L., Hummler E., Nenniger M., Pedrazzini T., Aubert J.F., Michel M.C., Yang M., Lembo G., Vecchione C., Mostardini M., Schmidt A., Beermann F., Cotecchia S.
ISSN
0027-8424 (Print)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
1997
Peer-reviewed
Oui
Volume
94
Numéro
21
Pages
11589-11594
Langue
anglais
Résumé
To investigate the functional role of different alpha1-adrenergic receptor (alpha1-AR) subtypes in vivo, we have applied a gene targeting approach to create a mouse model lacking the alpha1b-AR (alpha1b-/-). Reverse transcription-PCR and ligand binding studies were combined to elucidate the expression of the alpha1-AR subtypes in various tissues of alpha1b +/+ and -/- mice. Total alpha1-AR sites were decreased by 98% in liver, 74% in heart, and 42% in cerebral cortex of the alpha1b -/- as compared with +/+ mice. Because of the large decrease of alpha1-AR in the heart and the loss of the alpha1b-AR mRNA in the aorta of the alpha1b-/- mice, the in vivo blood pressure and in vitro aorta contractile responses to alpha1-agonists were investigated in alpha1b +/+ and -/- mice. Our findings provide strong evidence that the alpha1b-AR is a mediator of the blood pressure and the aorta contractile responses induced by alpha1 agonists. This was demonstrated by the finding that the mean arterial blood pressure response to phenylephrine was decreased by 45% in alpha1b -/- as compared with +/+ mice. In addition, phenylephrine-induced contractions of aortic rings also were decreased by 25% in alpha1b-/- mice. The alpha1b-AR knockout mouse model provides a potentially useful tool to elucidate the functional specificity of different alpha1-AR subtypes, to better understand the effects of adrenergic drugs, and to investigate the multiple mechanisms involved in the control of blood pressure.
Mots-clé
Animals, Aorta, Thoracic/drug effects, Aorta, Thoracic/physiology, Base Sequence, Blood Pressure/drug effects, Blood Pressure/physiology, Cricetinae, Female, Heart/physiology, Male, Mice, Mice, Inbred BALB C, Mice, Knockout, Molecular Sequence Data, Muscle Contraction/drug effects, Muscle, Smooth, Vascular/drug effects, Muscle, Smooth, Vascular/physiology, Myocardium/metabolism, Norepinephrine/pharmacology, Organ Specificity, Phenylephrine/pharmacology, Polymerase Chain Reaction, RNA, Messenger/biosynthesis, Receptors, Adrenergic, alpha-1/biosynthesis, Receptors, Adrenergic, alpha-1/deficiency, Transcription, Genetic
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 12:05
Dernière modification de la notice
20/08/2019 16:48
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