title: Response to catecholamine stimulation of polymorphisms of the beta-1 and beta-2 adrenergic receptors.
abstract: Previous studies have demonstrated that β-adrenergic receptor polymorphisms affect outcomes in patients with heart failure or after an acute coronary syndrome. Whether β-adrenergic polymorphisms influence catecholamine responses in patients with cardiovascular disease is not known. Cardiovascular responses to the β1-receptor agonist dobutamine and the β2-receptor agonist terbutaline were studied using gated blood pool scintigraphy in 21 patients on long-term β-blocker therapy. Heart rate (HR), stroke volume (SV), and cardiac output (CO) increased, and end-systolic volume decreased with dobutamine and terbutaline. Changes in HR and CO with dobutamine were higher for those with ≥1 β1 Arg389 allele than those homozygous for the Gly389 allele (change in HR 15 vs 1 beat/min, p = 0.02; change in CO 2.4 vs 1.0 L/min, p = 0.02). Increases in HR, CO, and SV with terbutaline were greater for those homozygous for the β2 Glu27 allele than those with ≥1 Gln27 allele (change in HR 13.7 vs 4.8 beats/min, p = 0.048; change in CO 3.1 vs 1.6 L/min, p = 0.034; change in SV 28.3 vs 14.8 ml, p = 0.045). Changes in CO and volume with terbutaline were greater in those with an ejection fraction <40% than in those with an ejection fraction ≥40%. In conclusion, β-receptor gene variants significantly influence inotropic and chronotropic responses to β-agonist exposure in patients on β-blocker therapy.
authors: Division of Cardiology, Department of Medicine, the Johns Hopkins University, Baltimore, Maryland, USA. rmclean5@jhmi.edu
authors: Rhondalyn C
authors: RC
authors: McLean
authors: Stacy W
authors: SW
authors: Baird
authors: Lewis C
authors: LC
authors: Becker
authors: Susan N
authors: SN
authors: Townsend
authors: Gary
authors: G
authors: Gerstenblith
authors: David A
authors: DA
authors: Kass
authors: Gordon F
authors: GF
authors: Tomaselli
authors: Steven P
authors: SP
authors: Schulman
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D000483:Alleles; D002395:Catecholamines / Q000494:pharmacology*; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects / Q000235:genetics; D011110:Polymorphism, Genetic / Q000187:drug effects*; D011379:Prognosis; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics* / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects / Q000235:genetics
chemical_list: D002395:Catecholamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D004247:DNA