Comparison of the effects of nadolol and bisoprolol on noradrenaline-evoked venoconstriction in man in vivo

Abstract

Aims. In an attempt to explore the possible involvement of venodilator β-adrenoceptors in the constrictor response of the human dorsal hand vein to noradrenaline, we examined the ability of nadolol, a non-selective β1/β2-adrenoceptor antagonist, and bisoprolol a selective β1-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-1) 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) log ED50s (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 β-adrenoceptors in the response. The mechanism underlying the antagonism of noradrenaline-evoked venoconstriction by bisoprolol remains to be elucidated.