This Article Full Text Full Text (PDF) All Versions of this Article: 44/5/776    most recent 01.HYP.0000145405.01113.0ev1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Townsend, S. A. Articles by Berkowitz, D. E. Search for Related Content PubMed PubMed Citation Articles by Townsend, S. A. Articles by Berkowitz, D. E. Related Collections Contractile function Animal models of human disease Cell signalling/signal transduction Genetically altered mice Receptor pharmacology Other Vascular biology

(Hypertension. 2004;44:776.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Critical Role for the -1B Adrenergic Receptor at the Sympathetic Neuroeffector Junction

Seth A. Townsend; Albert S. Jung; Yen Shi Gillian Hoe; Rafael Y. Lefkowitz; Shakil A. Khan; Christoper A. Lemmon; Robert W. Harrison; KwanghHo Lee; Lili A. Barouch; Susanna Cotecchia; Artin A. Shoukas; Daniel Nyhan; Joshua M. Hare; Dan E. Berkowitz

From the Departments of Anesthesiology/Critical Care Medicine (K.H.L., D.N., D.E.B.), Medicine (S.A.K., R.W.H., L.A.B., J.M.H.), and Biomedical Engineering (S.A.T., A.S.J., Y.S.G.H., R.Y.L., C.A.L., A.A.S., D.E.B.), Johns Hopkins University School of Medicine, Baltimore, MD; and the University of Lausanne, Switzerland (S.C.).

Correspondence to Dan E. Berkowitz, MD, Anesthesiology/CCM, Tower 711, Johns Hopkins Medical Institutions, 600 N Wolfe St, Baltimore, MD 21287. E-mail dberkowi{at}bme.jhu.edu

The -1 adrenergic receptors (₁ARs) are critical in sympathetically mediated vasoconstriction. The specific role of each ₁AR subtype in regulating vasoconstriction remains highly controversial. Limited pharmacological studies suggest that differential ₁AR responses may be the result of differential activation of junctional versus extrajunctional receptors. We tested the hypothesis that the _1BAR 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 _1BAR 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 _1BAR 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 ₁AR mesenteric microvascular contractile responses to endogenous norepinephrine (NE; elicited by electrical field stimulation 10 Hz) was markedly depressed in _1BAR 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 _1BAR KO and WT mice (22.4±7.3% versus 33.4±4.3%; NS). Collectively, these results demonstrate a critical role for the _1BAR in baroreceptor-mediated adrenergic signaling at the vascular neuroeffector junction. Moreover, _1BARs modulate inotropic responses to baroreceptor activation. The critical role for _1BAR in neuroeffector regulation of vascular tone and myocardial contractility has profound clinical implications for designing therapies for orthostatic intolerance.

Key Words: receptors, adrenergic alpha • hypotension • sympathetic nervous system • vasoconstriction

This article has been cited by other articles:

				L. Santhanam, H. K. Lim, H. K. Lim, V. Miriel, T. Brown, M. Patel, S. Balanson, S. Ryoo, M. Anderson, K. Irani, et al. Inducible NO Synthase Dependent S-Nitrosylation and Activation of Arginase1 Contribute to Age-Related Endothelial Dysfunction Circ. Res., September 28, 2007; 101(7): 692 - 702. [Abstract] [Full Text] [PDF]

				C. J. Daly, I. McGrath, S. Townsend, and D. E. Berkowitz The Role of the {alpha}1B-Adrenergic Receptor in Vascular Structure and Function Hypertension, June 1, 2005; 45(6): e20 - e21. [Full Text] [PDF]