Comparison of the effects of nadolol and bisoprolol on the isoprenaline-evoked dilatation of the dorsal hand vein in man

Abstract

Aims: We attempted to explore the possible differential involvement of beta-adrenoceptor subtypes in the dilator response of the human dorsal hand vein to isoprenaline by examining the ability of bisoprolol, a selective beta1-adrenoceptor antagonist, and nadolol, a nonselective beta1/beta2-adrenoceptor antagonist, to antagonize the response.

Methods: Twelve healthy male volunteers participated in four weekly sessions. In the preliminary session a dose-response curve to the vasoconstrictor effect of phenylephrine was constructed and the dose producing 50-75% maximal response was determined for each individual. In each of the remaining three (treatment) sessions, nadolol (40 mg), bisoprolol (5 mg) or placebo was ingested, and isoprenaline hydrochloride (3.33-1000 ng min(-1)) was infused locally into the dorsal hand vein along with a constant dose of phenylephrine hydrochloride (to preconstrict the 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 treatment session according to a double-blind balanced cross-over design. Systolic and diastolic blood pressure, and heart rate were also measured.

Results: Isoprenaline produced dose-dependent venodilatation which was antagonized by nadolol but remained unaffected by bisoprolol (ANOVA with repeated measures: P < 0.025; Dunnett's test: placebo vs nadolol, P < 0.01; placebo vs bisoprolol, P = NS). Mean log ED50 (ng min-1) was significantly increased in the presence of nadolol and remained unchanged in the presence of bisoprolol (ANOVA, P < 0.025; Dunnett's test: placebo vs nadolol, P < 0.005; placebo vs bisoprolol, P = NS; differences between mean log ED50 [95% CI]: placebo vs bisoprolol -0.11 [-0.38, 0.16], placebo vs nadolol 0.32[0.09, 0.72], bisoprolol vs nadolol -0.43 [-0.71, -0.15]). Mean Emax did not differ in the three treatment conditions.

Conclusions: The failure of bisoprolol to attenuate isoprenaline-evoked venodilatation in the human dorsal hand vein argues against the involvement of a beta1-adrenoceptor-mediated component in the isoprenaline-evoked venodilatory responses. The possibility cannot be excluded that the consequences of beta1-adrenoceptor blockade by bisoprolol might have been obscured by a possible venodilator effect of bisoprolol.

Figure 1

Dose–response curves for the venodilator effect of isoprenaline during local infusion into the superficial dorsal hand vein (cuff pressure 45 mmHg) 2 h after ingestion of placebo (○), bisoprolol 5 mg (▪), and nadolol 40 mg (▴); mean ± s.e. mean, n = 12. 100% response was defined as the recording during saline infusion with the cuff inflated.