IngentaConnect Comparison of the effects of nadolol and bisoprolol on the isopre...

Abstract:

Aims

We attempted to explore the possible differential involvement of β-adrenoceptor subtypes in the dilator response of the human dorsal hand vein to isoprenaline by examining the ability of bisoprolol, a selective β₁-adrenoceptor antagonist, and nadolol, a nonselective β₁/β₂-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 (anovawith 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 E_max 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 β₁-adrenoceptor-mediated component in the isoprenaline-evoked venodilatory responses. The possibility cannot be excluded that the consequences of β₁-adrenoceptor blockade by bisoprolol might have been obscured by a possible venodilator effect of bisoprolol.

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