Bisoprolol attenuates noradrenaline- and phenylephrine-evoked venoconstriction in man in vivo.

AIMS 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.