Effects of thyroid hormone on cardiac beta-adrenergic responsiveness in conscious baboons

被引:75
作者
Hoit, BD
Khoury, SF
Shao, YF
Gabel, M
Liggett, SB
Walsh, RA
机构
关键词
thyroid; receptors; adrenergic; beta; contractility;
D O I
10.1161/01.cir.96.2.592
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Many of the cardiovascular manifestations of thyroid hormone excess resemble those produced by sympathoadrenal stimulation. The objective of this study was to determine the effects of thyroid hormone excess on myocardial beta-adrenergic expression and responsiveness to infused agonists in the primate heart. Methods and Results The responses of left ventricular isovolumic contraction (dP/dt(max)) and relaxation (tau) during graded dobutamine infusion were studied both before and after 4 weeks of thyroid hormone administration in 8 chronically instrumented baboons. At matched (atrially paced) heart rates, thyroid hormone significantly increased resting dP/dt(max) (3073+/-1034 versus 2318+/-829 mm Hg/s, P<.05) and decreased tau (24.0+/-5.5 versus 28.2+/-5.4 ms, P<.05). The change from baseline for dP/dt(max) and tau in response to beta(1)-adrenergic stimulation was significant at each dobutamine dose (2.5 to 10 mu g.kg(-1).min(-1)), but when expressed as a percent change, it was similar before versus after thyroid hormone. Similar changes were found when beta(2)-adrenergic stimulation was produced by terbutaline infusion in three additional baboons. beta-Adrenergic receptor (PAR) expression was higher in five thyroxine-treated than in five control baboons (37.4+/-1.2 versus 15.7+/-3.2 fmol/mg, P<.001), and this was due to a greater increase in the beta(2)AR (5.9+/-1.5 to 20.6+/-1.2 fmol/mg, P<.001) than the beta(1)AR (9.7+/-1.7 to 16.8+/-0.1 fmol/mg, P<.01) subtype. Conclusions In the primate heart, thyroid hormone produces positive inotropic and lusitropic effects in the resting state and upregulates both beta(1)AR and beta(2)AR, with the beta(2)AR increase predominating. At equivalent rates, however, thyroid hormone excess does nor appear to enhance the sensitivity of left ventricular contractility and relaxation to either beta(1)- or beta(2)-adrenergic stimulation.
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页码:592 / 598
页数:7
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