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 badrenoceptor subtypes in the dilator response of the human dorsal hand vein to isoprenaline by examining the ability of bisoprolol, a selective b 1 -adrenoceptor antagonist, and nadolol, a nonselective b 1 /b 2 -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 x1 ) 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 ED 50 (ng min x1 ) was signi®cantly 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 ED 50 [95% CI]: placebo vs bisoprolol x0.11 [-0.38, 0.16

Mechanisms of β-adrenergic receptor–mediated venodilation in humans

“…In this study isoproterenol‐induced venodilation was unaffected by the selective β 1 ‐adrenergic receptor antagonist bisoprolol, suggesting no significant involvement of β 1 ‐adrenergic receptors. Our results are in agreement with recent studies reporting that responses of human veins to isoproterenol are mediated exclusively by β 2 ‐adrenergic receptors 12 , 28 , 33 …”

“…On 2 separate study days, every subject received orally either 5 mg of the selective β 1 ‐adrenergic receptor antagonist bisoprolol (Ratiopharm, Ulm, Germany) or placebo (university hospital pharmacy, University of Technology, Dresden, Germany) 90 minutes before the experiment was started. The dose of the selective β 1 ‐adrenergic receptor antagonist bisoprolol used in this study was selected on the basis of published reports on the effectiveness of this drug in humans 12 . The vein was preconstricted to 20% basal vein size with increasing doses of PE, and the ED 80 (the dose reducing basal vein size to about 20%) of PE was continuously coinfused together with 257 ng/min isoproterenol (isoproterenol hydrochloride; Abbott Laboratories, Chicago, Ill) for 50 minutes.…”

“…The dose of the selective ␤ 1 -adrenergic receptor antagonist bisoprolol used in this study was selected on the basis of published reports on the effectiveness of this drug in humans. 12 The vein was preconstricted to 20% basal vein size with increasing doses of PE, and the ED 80 (the dose reducing basal vein size to about 20%) of PE was continuously coinfused together with 257 ng/min iso-proterenol (isoproterenol hydrochloride; Abbott Laboratories, Chicago, Ill) for 50 minutes. The vein size was monitored every 10 minutes.…”

Comparison of the effects of venlafaxine, desipramine, and paroxetine on noradrenaline‐ and methoxamine‐evoked constriction of the dorsal hand vein

“…Some of these results have been communicated to the British Association Subjects were allocated to treatments and sessions according to a double-blind balanced design. Each for Psychopharmacology [8].…”

The role of venodilators in the perioperative management of heart failure

“…bisoprolol) do not inhibit ß 1 -mediated vasodilatation and may act as venodilators. 81 Direct inhibition of a 1 -adrenoceptors is thought to underlie the reduction in cardiac afterload associated with carvedilol. 10 Nebivolol is known to augment vascular NO release, 82 produce systemic vasodilatation 83,84 and reverse endothelial dysfunction in hypertensive patients.…”