The hemodynamic response to constant dobutamine infusion: the effect of ADRB1 389 polymorphism and sex. Issue 6 (June 2018)

• Record Type: Journal Article
• Authors: Yogev, Dotan; Basheer, Maamoun; Perlman, Amichai; Blotnick, Simcha; Caraco, Yoseph; Muszkat, Mordechai
• Is Part Of: Pharmaocogenetics and genomics. Volume 28:Issue 6(2018)
• Publication Date: 2018-06
• Subjects: β-1 adrenergic receptor -- dobutamine -- genetic polymorphism -- receptor desensitization -- sex differences; Pharmacogenetics -- Periodicals; Pharmacogenomics -- Periodicals; Genetic toxicology -- Periodicals; Biomedical genetics -- Periodicals; 615.7
• DOI: 10.1097/FPC.0000000000000338
• Languages: English
• ISSNs: 1744-6872

Abstract

Abstract : Objectives: Prolonged activation of the β-1 adrenergic receptor (ADRB1) is associated with receptor desensitization. This process has been suggested to have important pathophysiological and clinical implications in conditions such as congestive heart failure. The contribution of genetic factors to this process is a subject of ongoing research. We have previously shown that the ADRB1 389 polymorphism affects the response to incremental dose infusion of the ADRB agonist dobutamine. The aim of the current study was to determine whether the ADRB1 389 polymorphism affects the hemodynamic response to constant dose infusion of dobutamine in healthy patients. Patients and methods: Healthy patients were recruited according to their ADRB1 49 and 389 genotypes [15 Arg389Arg, 10 Gly389Arg, and 10 Gly389Gly patients (all Ser49Ser), 21 men and 14 women]. Following a standardized protocol of dose increase, 6 mcg/kg/min dobutamine was infused over 2 h. Heart rate (HR), blood pressure (BP), and active plasma renin (PR) were measured. Standardized exercise (1 min) was performed at three time points during infusion. Results: In all patients, resting systolic BP was significantly decreased during infusion [144.4±11.5 vs. 140.3±12.2 mmHg (mean±SD), P =0.007]. There was no change in HR, and PR following 120 min of dobutamine infusion. ADRB1 389 genotypes were not associated with HR, systolic BP, and PR changes during dobutamine infusion (all P >0.05, repeated measures analysis of variance). Sex was associated with response to dobutamine. Among women, but not in men, resting HR significantly increased, and diastolic blood pressure (DBP) significantly decreased during dobutamine infusion [HR: 76.0±7.3 to 86.3±17.5 beats per minute ( P =0.023), and DBP 78.5±8.49 mmHg to 72.36±6.16 ( P =0.041) (repeated measures analysis of variance)]. Conclusion: In healthy patients, the ADRB1 389 genotype was not associated with hemodynamic changes during constant dobutamine infusion. In women, but not in men, HR significantly increased and DBP decreased during 2 h of infusion.