Effects of nebivolol stereoisomers on the action of adrenaline on blood pressure, heart rate and blood levels of noradrenaline and DOPEG.
1. Nebivolol (a new beta 1-adrenoceptor blocking drug) has particular effects on the cardiovascular system, i.e. it induces hypotension without affecting cardiac function or increasing peripheral vascular resistances. In this study, we aimed to evaluate the effects of nebivolol and its stereoisomers on the actions of adrenaline (AD) at the cardiovascular level as well as at the prejunctional level (as ascertained by modification of noradrenaline (NA) and dihydroxyphenylglycol (DOPEG) plasma levels in the anaesthetized dog. 2. AD infusion (0.1 micrograms kg-1 min-1) did not induce statistically significant changes in mean blood pressure and heart rate; it caused a pronounced and sustained rise of AD levels, no significant alterations in NA levels and a marked, progressive and sustained increase in DOPEG levels. 3. Mean blood pressure was not affected by any of the nebivolol isomers. d- and dl-nebivolol in the two doses used (0.3 and 0.03 mg kg-1 in 15 min) caused a significant and dose-dependent decrease in heart rate. Plasma levels of AD and NA were not changed by any of the nebivolol isomers tested. However, all of them significantly reduced the increase in plasma levels of DOPEG induced by adrenaline infusion. 4. We conclude (1) that AD infusion in the dog facilitates NA release and that DOPEG is a good index of this effect; and (2) nebivolol appears to act at the prejunctional level, reducing the increase in NA release induced by adrenaline, as shown by the effect on DOPEG plasma levels.
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
N
N
Borges
F
F
Martel
D
D
Branco
W
W
Osswald
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000097:blood; D000068577:Nebivolol; D009638:Norepinephrine / Q000097:blood*; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D004837:Epinephrine