title: The common Arg389gly ADRB1 polymorphism affects heart rate response to the ultra-short-acting β(1) adrenergic receptor antagonist esmolol in healthy individuals.
abstract: 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 (P(ANOVA)=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.affiliation: Department of Medicine, Division of Clinical Pharmacology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. muszkatm@hadassah.org.il
authors.forename: Mordechai
authors.initials: M
authors.lastname: Muszkat
authors.forename: Assaf
authors.initials: A
authors.lastname: Hoofien
authors.forename: Esther
authors.initials: E
authors.lastname: Orlanski-Meyer
authors.forename: Hani
authors.initials: H
authors.lastname: Makhoul
authors.forename: Einav
authors.initials: E
authors.lastname: Porat
authors.forename: Eliad M
authors.initials: EM
authors.lastname: Davidson
authors.forename: Simcha
authors.initials: S
authors.lastname: Blotnick
authors.forename: Yoseph
authors.initials: Y
authors.lastname: Caraco
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000378:metabolism / Q000494:pharmacology*; D015444:Exercise; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology*; D018342:Receptors, Adrenergic, beta-1 / Q000737:chemistry / Q000235:genetics*; D016037:Single-Blind Method; D013610:Tachycardia / Q000188:drug therapy / Q000209:etiology*
chemical_list: C547787:ADRB1 protein, human; D058671:Adrenergic beta-1 Receptor Antagonists; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; C036604:esmolol