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Long‐term exposure to β 2 ‐receptor agonist specifically desensitizes β‐receptor—mediated venodilation
Author(s) -
Stein Michael,
Deegan Robert,
Wood Alastair J J
Publication year - 1993
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1993.130
Subject(s) - terbutaline , agonist , desensitization (medicine) , vasodilation , receptor , vascular smooth muscle , medicine , endocrinology , epinephrine , pharmacology , chemistry , smooth muscle , asthma
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 β 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 β 2 ‐receptor—mediated effects. We have therefore shown that dynamic regulation of vascular responsiveness by long‐term exposure to β 2 ‐receptor agonist occurs in humans. This selective desensitization of vascular β‐adrenergic responsiveness will result in mixed α‐ and β‐adrenergic agonists, such as epinephrine, becoming relatively more vasoconstrictive, and it also has important implications in blood pressure response to stress. Clinical Pharmacology and Therapeutics (1993) 54, 187–193; doi: 10.1038/clpt.1993.130