Critical Role for the α-1B Adrenergic Receptor at the Sympathetic Neuroeffector Junction
| Autor: | Shakil A. Khan, Christoper A. Lemmon, Susanna Cotecchia, Albert S. Jung, Lili A. Barouch, Artin A. Shoukas, Yen Shi Gillian Hoe, Kwangh Ho Lee, Daniel Nyhan, Rafael Y. Lefkowitz, Dan E. Berkowitz, Joshua M. Hare, Robert W. Harrison, Seth A. Townsend |
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| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Sympathetic nervous system Baroreceptor Adrenergic receptor Neuroeffector Blood Pressure In Vitro Techniques Neuroeffector junction Contractility Mice Norepinephrine Receptors Adrenergic alpha-1 Internal medicine Neuroeffector Junction Internal Medicine medicine Animals Carotid Stenosis Mice Knockout Denervation business.industry Baroreflex Mesenteric Arteries Carotid Arteries medicine.anatomical_structure Endocrinology Vasoconstriction medicine.symptom business |
| Zdroj: | Hypertension. 44:776-782 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/01.hyp.0000145405.01113.0e |
| Popis: | The α-1 adrenergic receptors (α 1 ARs) are critical in sympathetically mediated vasoconstriction. The specific role of each α 1 AR subtype in regulating vasoconstriction remains highly controversial. Limited pharmacological studies suggest that differential α 1 AR responses may be the result of differential activation of junctional versus extrajunctional receptors. We tested the hypothesis that the α 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 α 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 α 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 1 AR mesenteric microvascular contractile responses to endogenous norepinephrine (NE; elicited by electrical field stimulation 10 Hz) was markedly depressed in α 1B AR KO mice compared with WT (12.4±1.7% versus 21.5±1.2%; P 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 α 1B AR in baroreceptor-mediated adrenergic signaling at the vascular neuroeffector junction. Moreover, α 1B ARs modulate inotropic responses to baroreceptor activation. The critical role for α 1B AR in neuroeffector regulation of vascular tone and myocardial contractility has profound clinical implications for designing therapies for orthostatic intolerance. |
| Databáze: | OpenAIRE |
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