Comparison of the effects of nadolol and bisoprolol on noradrenaline-evoked venoconstriction in man in vivo.
OBJECTIVE
In an attempt to explore the possible involvement of venodilator beta-adrenoceptors in the constrictor response of the human dorsal hand vein to noradrenaline, we examined the ability of nadolol, a non-selective beta1/beta2-adrenoceptor antagonist, and bisoprolol a selective beta1-adrenoceptor antagonist, to potentiate the response.


METHODS
Twelve healthy male volunteers participated in three weekly sessions. In each session nadolol (40 mg), bisoprolol (5 mg) or placebo was ingested, and (-) noradrenaline acid tartrate (0.33-33.33 ng min ) was infused locally into the dorsal hand 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 treatments and sessions according to a double-blind balanced cross-over design. Systolic and diastolic blood pressure, and heart rate were also measured.


RESULTS
Noradrenaline produced dose-dependent venoconstriction which was antagonized by bisoprolol but remained unaffected by nadolol (ANOVA with repeated measures: F(2,22) = 5.07, P < 0.025; Dunnett's test: placebo vs nadolol; t = 0.35, df = 22, k = 3, NS; placebo vs bisoprolol; t = 2.83, df = 22, k = 3, P < 0.01). Mean (+/- s.e. mean) logED50s (ng min[-1]) were 0.44 +/- 0.15 (placebo), 0.73 +/- 0.11 (bisoprolol) and 0.50 +/- 0.21 (nadolol); mean (95% CI) differences were 0.29 (-0.005, 0.58) for placebo vs bisoprolol and 0.06 (-0.35, 0.46) for placebo vs nadolol. Both active drugs significantly (compared with placebo, P < 0.05) decreased (mean change from pretreatment +/- s.e. mean) heart rate (bisoprolol -16.08 +/- 2.01; nadolol -11.67 +/- 2.06) and systolic blood pressure (bisoprolol -15.0 +/- 0.80; nadolol -9.47 +/- 0.18).


CONCLUSIONS
The failure of nadolol and bisoprolol to potentiate noradrenaline-evoked venoconstriction argues against the involvement of masked venodilator beta-adrenoceptors in the response. The mechanism underlying the antagonism of noradrenaline-evoked venoconstriction by bisoprolol remains to be elucidated.
Abdelmawla
A H
AH
Department of Psychiatry, Queen's Medical Centre, Nottingham.
Langley
R W
RW
Szabadi
E
E
Bradshaw
C M
CM
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D017298:Bisoprolol / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D006225:Hand / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009248:Nadolol / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010919:Placebos; D014661:Vasoconstriction / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D010919:Placebos; D009248:Nadolol; D009638:Norepinephrine; D017298:Bisoprolol