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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
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“According to the flip side of this principle, excessive sympathetic activation down-regulates b-adrenergic receptors (Stein et al., 1993; Elfellah et al., 1998).”
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Autonomic control of the venous system in health and disease: effects of drugs
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β 2 -Adrenoceptor Polymorphism Determines Vascular Reactivity in Humans
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Clinical pharmacology, physiology and pathophysiology of superficial veins‐2.
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Cyclosporine Impairs Vasodilation Without Increased Sympathetic Activity in Humans
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Self-citationBraden, G. L., Germain, M. J., Mulhern, J. G., et al. (1998) · CHEST Journal · doi:10.1378/chest.114.2.380 · Cited by 19
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Successful epidural anaesthesia for Caesarean section in a patient with spondyloepiphyseal dysplasia
de Boer, H. D., Hemelaar, A. E. A., van Dongen, R. T. M., et al. (2001) · British Journal of Anaesthesia · doi:10.1093/bja/86.1.133 · Cited by 13
de Galan, B. E., Rietjens, S. J., Tack, C. J., van der Werf, S. P., Sweep, C. G. J. (., W. M. Lenders, J., & Smits, P. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030407 · Cited by 12
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Abdelmawla, A. H., Langley, R. W., Bradshaw, E., & Bradshaw, C. M. (1996) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00168702
“As there is evidence for venodilator/~2-adrenoceptors in the dorsal hand vein (Eichler et al. 1990; Stein et al. 1993), the potentiation of the venoconstrictor response to noradrenaline might possibly also reflect the blockade of masked /32-adrenoceptors (see Szabadi 1977).”
BackgroundUNIVERSIDADE FEDERAL DE GOIÁS PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE
Cristina, L., & Jacomini, L. (2010)
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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