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CLINICAL RESEARCH: ADRENORECEPTOR POLYMORPHISM

The Arg389Gly Beta₁-Adrenoceptor Polymorphism and Catecholamine Effects on Plasma-Renin Activity

Departments of Nephrology and Pathophysiology, University of Essen Medical School, Essen, Germany.

Manuscript received May 4, 2005; revised manuscript received August 11, 2005, accepted August 22, 2005.

^_* Reprint requests and correspondence: Dr. Otto-Erich Brodde, University of Essen Medical School, Departments of Nephrology and Pathophysiology, Hufelandstr. 55, D-45147 Essen, Germany. (Email: otto-erich.brodde{at}uni-essen.de).

OBJECTIVES: The purpose of this research was to find out whether, in humans, dobutamine-induced hemodynamic effects and increase in plasma-renin activity (PRA) might be beta₁-adrenoceptor (ß₁AR) genotype-dependent.

BACKGROUND: In vitro Arg389Gly-ß₁AR polymorphism exhibits decreased receptor signaling.

METHODS: We studied 10 male homozygous Arg389-ß₁AR subjects and 8 male homozygous Gly389ß₁AR subjects; to avoid influences of codon 49 polymorphism, all were homozygous Ser49-ß₁AR. Subjects were infused with dobutamine (1 to 6 µg/kg/min) with or without bisoprolol (10 mg orally) pretreatment, and PRA, heart rate, contractility, and blood pressure were assessed.

RESULTS: With regard to PRA, dobutamine increased PRA more potently in Arg389-ß₁AR versus Gly389-ß₁AR subjects. Bisoprolol markedly suppressed the dobutamine-induced PRA increase in Arg389- but only marginally in Gly389-ß₁AR subjects. With regard to hemodynamics, dobutamine caused larger heart rate and contractility increases and diastolic blood pressure decreases in Arg389- versus Gly389-ß₁AR subjects. Bisoprolol reduced dobutamine-induced heart rate and contractility increases and diastolic blood pressure decreases more potently in Arg389- versus Gly389-ß₁AR subjects.

CONCLUSIONS: Codon 389 ß₁AR polymorphism is a determinant not only of hemodynamic effects but also of PRA. Thus, ß₁AR polymorphisms may be useful for predicting therapeutic responses to ßAR-blocker treatment.

Abbreviations and Acronyms   ß1AR = beta1-adrenoceptor   BP = blood pressure   DBP = diastolic blood pressure   HR = heart rate   PRA = plasma-renin activity   QS2c = heart rate-corrected duration of the electromechanical systole   RAAS = renin-angiotensin-aldosterone system   SBP = systolic blood pressure   SNP = single nucleotide polymorphism

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