Comparison of the effects of nadolol and bisoprolol on the isoprenaline-evoked dilatation of the dorsal hand vein in man.
OBJECTIVE
We attempted to explore the possible differential involvement of beta-adrenoceptor subtypes in the dilator response of the human dorsal hand vein to isoprenaline by examining the ability of bisoprolol, a selective beta1-adrenoceptor antagonist, and nadolol, a nonselective beta1/beta2-adrenoceptor antagonist, to antagonize the response.


METHODS
Twelve healthy male volunteers participated in four weekly sessions. In the preliminary session a dose-response curve to the vasoconstrictor effect of phenylephrine was constructed and the dose producing 50-75% maximal response was determined for each individual. In each of the remaining three (treatment) sessions, nadolol (40 mg), bisoprolol (5 mg) or placebo was ingested, and isoprenaline hydrochloride (3.33-1000 ng min(-1)) was infused locally into the dorsal hand vein along with a constant dose of phenylephrine hydrochloride (to preconstrict the vein) 2 h after the ingestion of the drugs. Changes in vein diameter were monitored with the dorsal hand vein compliance technique. Subjects were allocated to treatment session according to a double-blind balanced cross-over design. Systolic and diastolic blood pressure, and heart rate were also measured.


RESULTS
Isoprenaline produced dose-dependent venodilatation which was antagonized by nadolol but remained unaffected by bisoprolol (ANOVA with repeated measures: P < 0.025; Dunnett's test: placebo vs nadolol, P < 0.01; placebo vs bisoprolol, P = NS). Mean log ED50 (ng min-1) was significantly increased in the presence of nadolol and remained unchanged in the presence of bisoprolol (ANOVA, P < 0.025; Dunnett's test: placebo vs nadolol, P < 0.005; placebo vs bisoprolol, P = NS; differences between mean log ED50 [95% CI]: placebo vs bisoprolol -0.11 [-0.38, 0.16], placebo vs nadolol 0.32[0.09, 0.72], bisoprolol vs nadolol -0.43 [-0.71, -0.15]). Mean Emax did not differ in the three treatment conditions.


CONCLUSIONS
The failure of bisoprolol to attenuate isoprenaline-evoked venodilatation in the human dorsal hand vein argues against the involvement of a beta1-adrenoceptor-mediated component in the isoprenaline-evoked venodilatory responses. The possibility cannot be excluded that the consequences of beta1-adrenoceptor blockade by bisoprolol might have been obscured by a possible venodilator effect of bisoprolol.
Abdelmawla
A H
AH
Psychopharmacology Unit, Division of Psychiatry, Queen's Medical Centre, Nottingham NG7 2UH.
Langley
R W
RW
Szabadi
E
E
Bradshaw
C M
CM
D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D017298:Bisoprolol / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006225:Hand / Q000098:blood supply*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009248:Nadolol / Q000008:administration & dosage / Q000494:pharmacology*; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D010919:Placebos; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins / Q000187:drug effects* / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D010919:Placebos; D010656:Phenylephrine; D009248:Nadolol; D007545:Isoproterenol; D017298:Bisoprolol