title: Beta 2-adrenoceptor-mediated intrinsic sympathomimetic activity of carteolol: an in vivo study.
abstract: The intrinsic sympathomimetic activity (ISA) of a beta-adrenoceptor blocker can be mediated by beta(1)- or beta(2)-adrenoceptors. The aim of this study was to characterize the ISA of the beta-adrenoceptor blocker carteolol in healthy volunteers. Two approaches were employed. First, we assessed the effects of carteolol (20, 40 or 80 mg p.o.) on blood pressure, heart rate and heart-rate corrected duration of electromechanical systole (QS(2)c, a measure of cardiac contractility) in the volunteers. Carteolol dose-dependently increased systolic blood pressure, heart rate and contractility and decreased diastolic blood pressure. The beta(1)-adrenoceptor blocker bisoprolol did not attenuate these carteolol effects, but rather enhanced the effects on heart rate and systolic blood pressure. Second, we treated volunteers for 7 days with 1 x 20 mg/day carteolol and assessed lymphocyte beta(2)-adrenoceptor density (by (-)-[(125)I]-iodocyanopindolol binding) and functional responsiveness (by 10 muM isoprenaline-induced increase in lymphocyte cyclic AMP content). Carteolol significantly reduced lymphocyte beta(2)-adrenoceptor density and function. After withdrawal of carteolol lymphocyte beta(2)-adrenoceptor density and function recovered only very slowly and had not returned to control levels 11 days after carteolol withdrawal. In conclusion, the fact that, on the one hand, the cardiovascular effects of carteolol were not attenuated by the beta(1)-adrenoceptor blocker bisoprolol and, on the other, carteolol significantly decreased lymphocyte beta(2)-adrenoceptor density and function is in favour of the idea that the ISA of carteolol is mediated by beta(2)-adrenoceptors. Involvement of an additional receptor site (e.g. the propranolol-resistant state of the beta(1)-adrenoceptor), however, cannot be excluded.
authors.affiliation: Department of Nephrology, University of Essen Medical School, 45147 Essen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bruck
authors.forename: Ulrike
authors.initials: U
authors.lastname: Poller
authors.forename: Hendrik
authors.initials: H
authors.lastname: Lüssenhop
authors.forename: Klaus
authors.initials: K
authors.lastname: Pönicke
authors.forename: Thomas
authors.initials: T
authors.lastname: Temme
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
authors.forename: Thomas
authors.initials: T
authors.lastname: Philipp
authors.forename: Otto-Erich
authors.initials: OE
authors.lastname: Brodde
mesh_terms: D058672:Adrenergic beta-2 Receptor Antagonists; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002354:Carteolol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D016037:Single-Blind Method; D013566:Sympathomimetics / Q000494:pharmacology*
chemical_list: D058672:Adrenergic beta-2 Receptor Antagonists; D018343:Receptors, Adrenergic, beta-2; D013566:Sympathomimetics; D002354:Carteolol