title: Differentiation of beta 1- and beta 2-adrenoceptor-mediated effects in humans.
abstract: To differentiate beta 1- and beta 2-adrenoceptor-mediated effects in humans, we studied the effects of a 2-wk treatment of 12 male volunteers with the selective beta 1-adrenoceptor antagonist bisoprolol (1 x 10 mg/day) and the beta 2-selective antagonist ICI 118,551 (3 x 25 mg/day) on lymphocyte beta 2-adrenoceptor density and responsiveness [10 microM l-isoproterenol (IPN) evoked adenosine 3',5'-cyclic monophosphate (cAMP) increase] as well as on exercise- and IPN-induced changes in lymphocyte beta 2-adrenoceptor density, blood pressure, heart rate, and plasma norepinephrine levels. ICI 118,551 administration increased lymphocyte beta 2-adrenoceptor density and responsiveness by approximately 50%, whereas bisoprolol had no effect. Dynamic exercise on a bicycle and infusion of graded doses of IPN led to an approximately 100% increase in lymphocyte beta 2-adrenoceptor density; this was abolished by ICI 118,551 but not affected by bisoprolol. ICI 118,551 markedly attenuated IPN-induced decrease in diastolic blood pressure but did not affect increase in systolic blood pressure, whereas bisoprolol had opposite effects. The IPN-induced increase in heart rate, however, was antagonized by both bisoprolol and (to a greater extent) ICI 118,551. Finally, ICI 118,551 completely abolished the IPN-induced increase in plasma norepinephrine levels, whereas bisoprolol had no effect. These results indicate that bisoprolol and ICI 118,551 are suitable tools to differentiate in humans beta 1- and beta 2-adrenoceptor-mediated effects.
authors.affiliation: Division of Renal and Hypertensive Diseases, University of Essen, Federal Republic of Germany.
authors.forename: O E
authors.initials: OE
authors.lastname: Brodde
authors.forename: A
authors.initials: A
authors.lastname: Daul
authors.forename: A
authors.initials: A
authors.lastname: Wellstein
authors.forename: D
authors.initials: D
authors.lastname: Palm
authors.forename: M C
authors.initials: MC
authors.lastname: Michel
authors.forename: J J
authors.initials: JJ
authors.lastname: Beckeringh
mesh_terms: D000328:Adult; D017298:Bisoprolol; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008214:Lymphocytes / Q000032:analysis; D008297:Male; D009638:Norepinephrine / Q000097:blood; D005082:Physical Exertion; D011412:Propanolamines / Q000097:blood / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012016:Reference Values
chemical_list: D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine; D017298:Bisoprolol