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Comparison of the effects of nadolol and bisoprolol on noradrenaline‐evoked venoconstriction in man in vivo
Author(s) -
Abdelmawla A. H.,
Langley R. W.,
Szabadi E.,
Bradshaw C. M.
Publication year - 1998
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1998.00683.x
Subject(s) - bisoprolol , nadolol , placebo , medicine , antagonist , anesthesia , volunteer , blood pressure , propranolol , alternative medicine , receptor , pathology , agronomy , biology
Aims In an attempt to explore the possible involvement of venodilator β‐adrenoceptors in the constrictor response of the human dorsal hand vein to noradrenaline, we examined the ability of nadolol, a non‐selective β 1 /β 2 ‐adrenoceptor antagonist, and bisoprolol a selective β 1 ‐adrenoceptor antagonist, to potentiate the response.Methods Twelve healthy male volunteers participated in three weekly sessions. In each session nadolol (40 mg), bisoprolol (5 mg) or placebo was ingested, and (‐) noradrenaline acid tartrate (0.33–33.33 ng min −1 ) was infused locally into the dorsal hand 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 treatments and sessions according to a double‐blind balanced cross‐over design. Systolic and diastolic blood pressure, and heart rate were also measured.Results Noradrenaline produced dose‐dependent venoconstriction which was antagonized by bisoprolol but remained unaffected by nadolol (ANOVA with repeated measures: F (2,22)=5.07, P <0.025; Dunnett's test: placebo vs nadolol; t =0.35, df=22, k =3, NS; placebo vs bisoprolol; t =2.83, df=22, k =3, P <0.01 ). Mean (±s.e. mean) log E D 50 s (ng min −1 ) were 0.44±0.15 (placebo), 0.73±0.11 (bisoprolol) and 0.50±0.21 (nadolol); mean (95% CI) differences were 0.29 (−0.005, 0.58) for placebo vs bisoprolol and 0.06 (−0.35, 0.46) for placebo vs nadolol. Both active drugs significantly (compared with placebo, P<0.05) decreased (mean change from pretreatment±s.e. mean) heart rate (bisoprolol −16.08±2.01; nadolol −11.67±2.06) and systolic blood pressure (bisoprolol −15.0±0.80; nadolol −9.47±0.18).Conclusions The failure of nadolol and bisoprolol to potentiate noradrenaline‐evoked venoconstriction argues against the involvement of masked venodilator β‐adrenoceptors in the response. The mechanism underlying the antagonism of noradrenaline‐evoked venoconstriction by bisoprolol remains to be elucidated.