BISOPROLOL ATTENUATES NORADRENALINE-EVOKED AND PHENYLEPHRINE-EVOKED VENOCONSTRICTION IN MAN IN-VIVO

Aims The aim of this study was to examine the effects of bisoprolol (B IS), a selective beta 1-adrenoceptor antagonist without partial agonis tic activity, on noradrenaline- and phenylephrine-evoked venoconstrict ion in man using the dorsal hand vein compliance technique. Methods Tw elve healthy male volunteers participated in three weekly experimental sessions. Subjects were allocated to treatments and sessions on a dou ble-blind basis. In each session either BIS 5 mg (BIS5), or BIS 10 mg (BIS10), or placebo was administered orally, and nonadrenaline acid ta rtrate (0.1-33.33 ng min(-1)) followed by phenylephrine hydrochloride (0.033-10 mu g min(-1)) was infused into the dorsal hand vein. Systoli c and diastolic blood pressure and heart rate were also measured. Resu lts Both noradrenaline and phenylephrine produced dose-dependent venoc onstriction: the geometric mean ED50 for noradrenaline was 3.21 ng min (-1) and for phenylephrine 135.04 ng min(-1); the potency ratio (norad renaline/phenylephrine) was 42. Both BIS5 and BIS10 significantly decr eased the venoconstriction to noradrenaline (ANOVA; P < 0.005), and to phenylephrine (ANOVA; P < 0.001). The antagonism of the venoconstrict or responses was also reflected in a significant increase in logED(50) 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 systo lic blood pressure (ANOVA; P < 0.0025). Conclusions Bisoprolol can ant agonize alpha(1)-adrenoceptor mediated venoconstriction in the human d orsal hand vein in vive through a mechanism which remains to be elucid ated.