In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 285, No. 5 ( 2003-11), p. H2034-H2038
Abstract:
In subjects heterozygous for Thr164Ile β 2 -adrenoceptor (β 2 AR) polymorphism, cardiac responses to β 2 AR agonist stimulation are blunted. In this study, we investigated agonist-induced desensitization of Thr164Ile β 2 ARs. For this purpose, we assessed in six subjects with heterozygous Thr164Ile β 2 ARs and in 10 subjects with homozygous wild-type (WT) β 2 ARs the effects of 2-wk oral treatment with 3 × 5 mg/day terbutaline on terbutaline infusion-induced increases in heart rate (HR) and contractility [measured as shortening of HR-corrected duration of electromechanical systole (QS 2 c)]. Compared with WT β 2 AR subjects, Thr164Ile subjects exhibited a blunted terbutaline-induced maximum increase in HR (WT 32 ± 4 beats/min, Thr164Ile 19 ± 3 beats/min, P 〈 0.05) and contractility (WT –54 ± 2 ms, Thr164Ile –37 ± 6 ms, P 〈 0.05). Two-week oral terbutaline treatment desensitized cardiac β 2 AR responses to terbutaline infusion (increase in HR: WT 10 ± 2 beats/min, Thr164Ile 8 ± 4 beats/min; increase in contractility: WT –22 ± 5 ms Thr164Ile: –17 ± 6 ms); however, the extent of desensitization was larger in WT than Thr164Ile β 2 AR subjects. Thus, after 2-wk oral terbutaline treatment cardiac, β 2 AR responses did not differ anymore between WT and Thr164Ile β 2 AR subjects. We conclude that agonist-induced desensitization of cardiac β 2 ARs is more pronounced in WT than Thr164Ile subjects. Thus cardiac Thr164Ile subjects appear to be somewhat protected against agonist-induced desensitization.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00324.2003
Language:
English
Publisher:
American Physiological Society
Publication Date:
2003
detail.hit.zdb_id:
1477308-9
SSG:
12
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