Functional effects of β₁-adrenoceptor polymorphisms on the hemodynamic response to dobutamine with and without β-blocker administration.
BACKGROUND
The relevance of the Arg389Gly- and Ser49Gly-β₁-adrenoceptor (AR) polymorphisms for cardiovascular function and pharmacotherapy is controversial.


METHODS
Out of 38 healthy male volunteers who were screened for both types of the β₁-AR polymorphism 23 subjects underwent dobutamine stress echocardiography at baseline, after administration of metoprolol succinate (n = 18, 190 mg/day) and 44 h after abrupt termination of the β-blocker (n = 17). Heart rate (HR), systolic blood pressure (SAP), HR-corrected left ventricular circumferential fiber shortening (VCF(C)), cardiac output (CO), systemic vascular resistance (SVR) and left ventricular end-systolic meridional wall stress (EsMWS) were measured. β₁-AR gene polymorphisms were analyzed by TaqMan-PCR.


RESULTS
Genotype frequency distributions and allele frequencies of the Gly389Arg and Ser49Gly polymorphisms of the β₁-AR were similar to published data. Although body surface area was similar for Arg/Arg subjects and Gly carriers the latter group revealed smaller left ventricular end-diastolic (-0.4 cm, p = 0.04) and end-systolic LV dimensions (-0.4 cm, p = 0.01). During dobutamine stimulation before, during and after termination of metoprolol coadministration no significant effect of the Arg389Gly-β₁-AR polymorphism on HR, SAP, CO and VCF(c) was detected. In contrast, SVR (p = 0.01) and EsMWS (p = 0.04) were significantly higher in Arg/Arg subjects. The VCF(C)-EsMWS regressions were similar for both groups, but revealed a minutely higher baseline contractility in the Arg/Arg group (p < 0.01). The β₁-AR Ser49Gly polymorphism had no effect on any of the measured parameters.


CONCLUSIONS
Although the Arg389Gly-β₁-AR polymorphism has only minor relevance for LV contractility it may impact left ventricular size and afterload. The Ser49Gly-β₁-AR polymorphism has no relevant effect on LV geometry or function.
Kindermann
Michael
M
Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Kirrberger Strasse, 66421, Homburg/Saar, Germany. Michael.Kindermann@t-online.de
Seeland
Ute
U
Ruhnke
Patrick
P
Böhm
Michael
M
Maack
Christoph
C
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000328:Adult; D004280:Dobutamine / Q000008:administration & dosage*; D004338:Drug Combinations; D005080:Exercise Test; D006352:Heart Ventricles / Q000000981:diagnostic imaging* / Q000187:drug effects; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D014463:Ultrasonography; D014665:Vasodilator Agents / Q000008:administration & dosage; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D004338:Drug Combinations; D018342:Receptors, Adrenergic, beta-1; D014665:Vasodilator Agents; D004280:Dobutamine
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