期刊
PHARMACOGENETICS
卷 11, 期 3, 页码 199-205出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00008571-200104000-00003
关键词
beta(1)-adrenoceptor polymorphism; heart rate; systolic time intervals; exercise
beta (1)-adrenoceptors play a pivotal role in regulating contractility and heart: rate in the human heart. Recently, a polymorphism of the beta (1)-adrenoceptor has been detected: at amino acid position 389 either Gly or Arg has been found with the Gly(389) exhibiting reduced responsiveness upon agonist-induced stimulation in vitro. In order to find out whether the Gly(389) polymorphism exhibits blunted responsiveness also in vivo we studied, in healthy volunteers, the effects of exercise on heart rate and heart rate-corrected duration of electromechanical systole (QS(2)c as a measure of inotropism) which, in humans, is mediated by beta (1)-adrenoceptors stimulation, Twenty-four healthy volunteers (12 female, 12 male) homozygous for the Gly(389) or Arg(389) exercised on a bicycle in supine position (25, 50, 75 and 100 W for 5 min each), and heart rate and QS(2)c were assessed; in addition, plasma renin activity (PRA) was determined which is also regulated by beta (1)-adrenoceptors in humans, Exercise caused work-load dependent increases in heart rate and PRE, and shortening of QS(2)c; however, these changes were not significantly different between the Gly(389) and Arg(389) polymorphism Thus, these three beta (1)-adrenoceptor responses did not differ between volunteers with the Arg(389) versus the Gly(389) polymorphism. Intragroup analysis, however, revealed that exercise induced increase in heart rate and shortening of QS(2)c were higher in female than in male volunteers. In conclusion our data do not support the idea that the reduced responsiveness of Gly(389) against agonist-induced stimulation observed in vitro is of major functional importance in vivo. Pharmacogenetics 11:199-205 (C) 2001 Lippincott Williams & Wilkins.
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