β1-Adrenoceptors (AR) play a pivotal role in regulating contractility and heart rate (HR) in the human heart. Recently, a polymorphism of the β1-AR has been detected: at amino acid position 389 either Gly or Arg has been found with the Gly389 exhibiting reduced responsiveness upon agonist induced stimulation in vitro. In order to find out whether the Gly389 polymorphism exhibits blunted responsiveness also in vivo we studied, in healthy volunteers, the effects of exercise on HR and HR-corrected duration of electromechanical systole (QS2c- as a measure of inotropism) which, in humans, is mediated by β1-AR stimulation. 24 healthy volunteers (12 female, 12 male) homozygous for the Gly389 or Arg389 polymorphism of the β1-Adrenoceptor exercised on a bicycle in supine position (25, 50, 75 and 100 Watt for 5 min each), and HR and QS2c were assessed; in addition, plasma renin activity (PRA) was determined which, in humans, is also regulated by β1-AR. Exercise caused work-load dependent increases in HR and PRA, and shortening of QS2c. These changes were, however, not significantly different between the Gly389 and Arg389 polymorphism. Thus, these three β1-AR responses did not differ between volunteers with the Arg389 vs. the Gly389 polymorphism. Intragroup analysis, however, revealed that exercise induced increase in HR and shortening of QS2c were higher in female than in male volunteers. In conclusion: our data do not support the idea that the reduced responsiveness of Gly389 against agonist-induced stimulation observed in vitro is of major functional importance in vivo. |