Document Detail


Relationship between the sympatholytic action of nebivolol and hypotension.
MedLine Citation:
PMID:  1383620     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nebivolol, a chemically novel beta 1-adrenoceptor antagonist, acutely lowers blood pressure in spontaneously hypertensive rats, anaesthetised normotensive dogs, and hypertensive patients. We have investigated the actions of dl-nebivolol in five conscious normotensive rabbits (sham, mean blood pressure (BP) of 82.2 +/- 4.1 mm Hg, mean +/- SEM) and four hypertensive rabbits (renal wrap hypertension) (wrap, mean BP of 117.6 +/- 1.5 mm Hg). Nebivolol (1 mg/kg i.v.) did not significantly lower the BP or heart rate in either group 30 min after injection. In the same rabbits, on another day, after autonomic blockade (mecamylamine), nebivolol (0.1, 0.3, and 1.0 mg/kg i.v.) right shifted the bolus i.v. isoproterenol tachycardia dose-response curves by dose ratios of 5, 18, and 90 in sham rabbits, respectively, and 5, 11, and 23 in wrap rabbits, respectively, indicating significant cardiac beta 1-adrenoceptor antagonism. In guinea pig isolated right atria pretreated with atropine (1 microM) and desipramine (DMI, 0.1 microM), norepinephrine concentration-response curves were antagonised competitively by nebivolol (3-100 nM), giving a pKb of 7.90. In separate atria without DMI pretreatment, neither nebivolol (100 nM) nor propranolol (100 nM) had any significant effect on the increase in the rate of norepinephrine efflux following electrical field stimulation (0.5-2 Hz, 3 min). These findings suggest that at concentrations of nebivolol that show substantial beta 1-adrenoceptor antagonism, there is no evidence of hypotension or bradycardia nor additional effects on cardiac norepinephrine release. Why nebivolol lowers blood pressure in some species but not in the conscious rabbit is not known.
Authors:
J E Ward; P Coles; H Cox; G Eisenhofer; J A Angus
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  20     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1992 Jul 
Date Detail:
Created Date:  1992-11-04     Completed Date:  1992-11-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  115-24     Citation Subset:  IM    
Affiliation:
Baker Medical Research Institute, Prahran, Victoria, Australia.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / pharmacology
Animals
Antihypertensive Agents / pharmacology
Benzopyrans / administration & dosage,  pharmacology*
Blood Pressure / drug effects*
Dose-Response Relationship, Drug
Ethanolamines / administration & dosage,  pharmacology*
Female
Guinea Pigs
Heart Rate / drug effects*
Hypertension / physiopathology*
Isoproterenol / pharmacology
Male
Mecamylamine / pharmacology
Myocardium / metabolism
Norepinephrine / metabolism*
Propranolol / pharmacology
Rabbits
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Antihypertensive Agents; 0/Benzopyrans; 0/Ethanolamines; 51-41-2/Norepinephrine; 525-66-6/Propranolol; 60-40-2/Mecamylamine; 7683-59-2/Isoproterenol; 99200-09-6/nebivolol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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