Critical role for the alpha-1B adrenergic receptor at the sympathetic neuroeffector junction.

Détails

ID Serval
serval:BIB_B9AB8B765BCA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Critical role for the alpha-1B adrenergic receptor at the sympathetic neuroeffector junction.
Périodique
Hypertension
Auteur(s)
Townsend S.A., Jung A.S., Hoe Y.S., Lefkowitz R.Y., Khan S.A., Lemmon C.A., Harrison R.W., Lee K., Barouch L.A., Cotecchia S., Shoukas A.A., Nyhan D., Hare J.M., Berkowitz D.E.
ISSN
1524-4563 (Electronic)
ISSN-L
0194-911X
Statut éditorial
Publié
Date de publication
2004
Volume
44
Numéro
5
Pages
776-782
Langue
anglais
Résumé
The alpha-1 adrenergic receptors (alpha(1)ARs) are critical in sympathetically mediated vasoconstriction. The specific role of each alpha(1)AR subtype in regulating vasoconstriction remains highly controversial. Limited pharmacological studies suggest that differential alpha(1)AR responses may be the result of differential activation of junctional versus extrajunctional receptors. We tested the hypothesis that the alpha(1B)AR subtype is critical in mediating sympathetic junctional neurotransmission. We measured in vivo integrated cardiovascular responses to a hypotensive stimulus (induced via transient bilateral carotid occlusion [TBCO]) in alpha(1B)AR knockout (KO) mice and their wild-type (WT) littermates. In WT mice, after dissection of the carotid arteries and denervation of aortic baroreceptor buffering nerves, TBCO produced significant pressor and positive inotropic effects. Both responses were markedly attenuated in alpha(1B)AR KO mice (change systolic blood pressure 46+/-8 versus 11+/-2 mm Hg; percentage change in the end-systolic pressure-volume relationship [ESPVR] 36+/-7% versus 12+/-2%; WT versus KO; P<0.003). In vitro alpha(1)AR mesenteric microvascular contractile responses to endogenous norepinephrine (NE; elicited by electrical field stimulation 10 Hz) was markedly depressed in alpha(1B)AR KO mice compared with WT (12.4+/-1.7% versus 21.5+/-1.2%; P<0.001). In contrast, responses to exogenous NE were similar in alpha(1B)AR KO and WT mice (22.4+/-7.3% versus 33.4+/-4.3%; NS). Collectively, these results demonstrate a critical role for the alpha(1B)AR in baroreceptor-mediated adrenergic signaling at the vascular neuroeffector junction. Moreover, alpha(1B)ARs modulate inotropic responses to baroreceptor activation. The critical role for alpha(1B)AR in neuroeffector regulation of vascular tone and myocardial contractility has profound clinical implications for designing therapies for orthostatic intolerance.
Mots-clé
Animals, Baroreflex/physiology, Blood Pressure/physiology, Carotid Arteries/physiology, Carotid Stenosis/physiopathology, Mesenteric Arteries/physiology, Mice, Mice, Knockout, Neuroeffector Junction/physiology, Norepinephrine/pharmacology, Norepinephrine/physiology, Receptors, Adrenergic, alpha-1/genetics, Receptors, Adrenergic, alpha-1/physiology, Vasoconstriction/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 15:27
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