title: Bisoprolol attenuates noradrenaline- and phenylephrine-evoked venoconstriction in man in vivo.
abstract: OBJECTIVE
  The aim of this study was to examine the effects of bisoprolol (BIS), a selective beta1-adrenoceptor antagonist without partial agonistic activity, on noradrenaline- and phenylephrine-evoked venoconstriction in man using the dorsal hand vein compliance technique.
  
  
  METHODS
  Twelve healthy male volunteers participated in three weekly experimental sessions. Subjects were allocated to treatments and sessions on a double-blind basis. In each session either BIS 5 mg (BIS5), or BIS 10 mg (BIS10), or placebo was administered orally, and noradrenaline acid tartrate (0.1-33.33 ng min (-1) followed by phenylephrine hydrochloride (0.033-10 microg min(-l)) was infused into the dorsal hand vein. Systolic and diastolic blood pressure and heart rate were also measured.
  
  
  RESULTS
  Both noradrenaline and phenylephrine produced dose-dependent venoconstriction: the geometric mean ED50 for noradrenaline was 3.21 ng min(-1) and for phenylephrine 135.04 ng min(-1); the potency ratio (noradrenaline/phenylephrine) was 42. Both BIS5 and BIS10 significantly decreased the venoconstriction to noradrenaline (ANOVA; P<0.005), and to phenylephrine (ANOVA; P<0.001). The antagonism of the venoconstrictor responses was also reflected in a significant increase in logED50 values for both noradrenaline (ANOVA; P<0.005), and phenylephrine (ANOVA; P<0.0025) in the presence of both doses of BIS. Both doses of BIS significantly decreased heart rate (ANOVA; P<0.0001), and systolic blood pressure (ANOVA; P<0.0025).
  
  
  CONCLUSIONS
  Bisoprolol can antagonize alpha1-adrenoceptor mediated venoconstriction in the human dorsal hand vein in vivo through a mechanism which remains to be elucidated.
authors.affiliation: Department of Psychiatry, Queen's Medical Centre, Nottingham, UK.
authors.forename: A H
authors.initials: AH
authors.lastname: Abdelmawla
authors.forename: R W
authors.initials: RW
authors.lastname: Langley
authors.forename: E
authors.initials: E
authors.lastname: Szabadi
authors.forename: C M
authors.initials: CM
authors.lastname: Bradshaw
mesh_terms: D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D017298:Bisoprolol / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003187:Compliance; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004336:Drug Antagonism; D006225:Hand / Q000098:blood supply*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009638:Norepinephrine; D017298:Bisoprolol