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The common Arg389gly ADRB1 polymorphism affects heart rate response to the ultra-short-acting β1 adrenergic receptor antagonist esmolol in healthy individuals.
MedLine Citation:
PMID:  23114278     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The β1-adrenergic receptor (β1AR) Arg389Gly polymorphism affects responses to orally administered β1AR antagonists (β-blockers) in vivo. However, the effect of this polymorphism on the early heart rate response to β-blockers has not been evaluated. The aim of this study was to determine the effect of the Arg389Gly polymorphism on the inhibition of exercise-induced tachycardia by esmolol, an ultra-short-acting intravenously administered β1AR antagonist. Healthy nonsmoking White individuals were enrolled on the basis of their ADRB1 genotype, including carriers of 0, 1 or 2 Arg389 alleles (n=9 in each group, total 27, 18 men). Placebo and esmolol were infused consecutively for 10 min each, separated by 30 min. At the end of each infusion, participants performed dynamic handgrip exercise. Heart rate and blood pressure were compared among three ADRB1 genotypes. Carriers of 0, 1, or 2 Arg389 alleles varied significantly in both exercise-induced tachycardia during esmolol (PANOVA=0.030) and esmolol inhibition of exercise-induced tachycardia [0.78±7.70, 5.11±4.05, 10.22±9.78 bpm, respectively (P=0.014)]. The early effect of esmolol on exercise-induced tachycardia was significantly greater among Arg389 than in Gly389 homozygote healthy individuals (NCT01388036).
Authors:
Mordechai Muszkat; Assaf Hoofien; Esther Orlanski-Meyer; Hani Makhoul; Einav Porat; Eliad M Davidson; Simcha Blotnick; Yoseph Caraco
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-31
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  -     ISSN:  1744-6880     ISO Abbreviation:  Pharmacogenet. Genomics     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-11-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
aDepartment of Medicine, Division of Clinical Pharmacology bDepartment of Anesthesiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
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