COMPARISON OF THE EFFECTS OF NADOLOL AND BISOPROLOL ON NORADRENALINE-EVOKED VENOCONSTRICTION IN MAN IN-VIVO

Aims In an attempt to explore the possible involvement of venodilator beta-adrenoceptors in the constrictor response of the human dorsal han d vein to noradrenaline, we examined the ability of nadolol, a non-sel ective beta(1)/beta(2)-adrenoceptor antagonist, and bisoprolol a selec tive beta(1)-adrenoceptor antagonist, to potentiate the response. Meth ods Twelve healthy male volunteers participated in three weekly sessio ns. 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. S ystolic and diastolic blood pressure, and heart rate were also measure d. Results Noradrenaline produced dose-dependent venoconstriction whic h was antagonized by bisoprolol but remained unaffected by nadolol (AN OVA 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 bisoprol ol; t = 2.83, df = 22, k = 3, P < 0.01). Mean (+/- s.e. mean) log ED(5 0)s (ng min(-1)) were 0.44 +/- 0.15 (placebo), 0.73 +/- 0.11 (bisoprol ol) 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 pla cebo vs nadolol. Both active drugs significantly (compared with placeb o, P < 0.05) decreased (mean change from pretreatment +/- s.e. mean) h eart rate (bisoprolol -16.08 +/- 2.01; nadolol -11.67 +/- 2.06) and sy stolic blood pressure (bisoprolol -15.0 +/- 0.80; nadolol -9.47 +/- 0. 18). Conclusions The failure of nadolol and bisoprolol to potentiate n oradrenaline-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.