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Functional effects of β1-adrenoceptor polymorphisms on the hemodynamic response to dobutamine with and without β-blocker administration

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Abstract

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 (VCFC), 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 VCFc was detected. In contrast, SVR (p = 0.01) and EsMWS (p = 0.04) were significantly higher in Arg/Arg subjects. The VCFC–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.

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Acknowledgments

The study was supported by the Emmy Noether-Programm (to C.M.) and the Klinische Forschergruppe KFO196 (to C.M. and M.B.) by the Deutsche Forschungsgemeinschaft.

Conflict of interest

There are no conflicts of interest to disclose.

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Authors and Affiliations

  1. Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Kirrberger Straße, 66421, Homburg/Saar, Germany

    Michael Kindermann, Ute Seeland, Patrick Ruhnke, Michael Böhm & Christoph Maack

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  1. Michael Kindermann
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  2. Ute Seeland
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Correspondence to Michael Kindermann.

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Kindermann, M., Seeland, U., Ruhnke, P. et al. Functional effects of β1-adrenoceptor polymorphisms on the hemodynamic response to dobutamine with and without β-blocker administration. Clin Res Cardiol 100, 129–137 (2011). https://doi.org/10.1007/s00392-010-0221-z

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