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Long-term exposure to β2-receptor agonist specifically desensitizes β-receptor—mediated venodilation
Abstract
Desensitization of human vascular smooth muscle has not been shown after long-term exposure to agonist. Using the dorsal hand vein compliance technique, we measured the vascular sensitivity to isoproterenol, alprostadil, and nitroglycerin. Nine volunteers were studied after receiving no treatment or after 7 days of the beta 2-agonist terbutaline (5 mg three times daily). Terbutaline pretreatment desensitized the vascular response to isoproterenol, resulting in a fourfold increase in the dose of isoproterenol required to produce 10% vasodilation (geometric mean after terbutaline, 100.8 ng/min; without terbutaline, 26.7 ng/min; p < 0.001). The desensitization was specific for beta 2-receptor-mediated effects. We have therefore shown that dynamic regulation of vascular responsiveness by long-term exposure to beta 2-receptor agonist occurs in humans. This selective desensitization of vascular beta-adrenergic responsiveness will result in mixed alpha- and beta-adrenergic agonists, such as epinephrine, becoming relatively more vasoconstrictive, and it also has important implications in blood pressure response to stress.
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“previous reports showing that exposure to betaadrenergic agonists in humans may lead to attenuation of beta-adrenergic receptor responses (35, 36)”
From Plasma Epinephrine Contributes to the Development of Experimental Hypoglycemia-Associated Autonomic Failure (2020) · cites this paper as [35]
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Dishy, V., Sofowora, G. G., Xie, H., Kim, R. B., Byrne, D. W., Stein, C. M., & Wood, A. J. J. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa010819 · Cited by 363
Self-citationMechanisms underlying development of spatially distributed chronic pain (fibromyalgia)
Vierck, C. J. (2006) · Pain · doi:10.1016/j.pain.2006.06.001 · Cited by 297
“According to the flip side of this principle, excessive sympathetic activation down-regulates b-adrenergic receptors (Stein et al., 1993; Elfellah et al., 1998).”
BackgroundNelson, H. S. (1995) · New England Journal of Medicine · doi:10.1056/nejm199508243330807 · Cited by 249
Autonomic control of the venous system in health and disease: effects of drugs
Pang, C. C. Y. (2001) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(01)00138-3 · Cited by 219
β 2 -Adrenoceptor Polymorphism Determines Vascular Reactivity in Humans
Cockcroft, J. R., Gazis, A., Cross, D. J., Wheatley, A. P., Dewar, J. C., Hall, I. P., & Noon, J. P. (2000) · Hypertension · doi:10.1161/01.hyp.36.3.371 · Cited by 160
Metadata
- Authors
- Stein, M., Deegan, R., & Wood, A. J. J.
- Affiliations
- Vanderbilt University (US)
- ORCID
- Deegan, Robert
- Venue
- Clinical Pharmacology and Therapeutics
- Publisher
- Wiley
- Published
- 1993-08
- Volume
- 54
- Issue
- 2
- Pages
- 187-193
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- OpenAlex
- W2094207175
- Cited by
- 29
- References
- 0
- Citations by year
- 2020: 1
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- terbutaline, beta2-adrenergic agonists, venodilation, vascular smooth muscle, isoproterenol, prostaglandin E1, nitroglycerin, beta-adrenergic responsiveness, blood pressure response to stress
- MeSH terms
- Adrenergic beta-Agonists, Alprostadil, Dose-Response Relationship, Drug, Heart, Hemodynamics, Humans, Isoproterenol, Receptors, Adrenergic, beta, Terbutaline, Exercise
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