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


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 beta1-adrenergic stimulation was significant at each dobutamine dose (2.5 to 10 microg x kg(-1) x min(-1)), but when expressed as a percent change, it was similar before versus after thyroid hormone. Similar changes were found when beta2-adrenergic stimulation was produced by terbutaline infusion in three additional baboons. beta-Adrenergic receptor (betaAR) 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 beta2AR (5.9+/-1.5 to 20.6+/-1.2 fmol/mg, P<.001) than the beta1AR (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 beta1AR and beta2AR, with the beta2AR increase predominating. At equivalent rates, however, thyroid hormone excess does not appear to enhance the sensitivity of left ventricular contractility and relaxation to either beta1- or beta2-adrenergic stimulation.
Hoit
B D
BD
Division of Cardiology, University of Cincinnati Medical Center, Ohio 45267-0542, USA.
Khoury
S F
SF
Shao
Y
Y
Gabel
M
M
Liggett
S B
SB
Walsh
R A
RA
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000818:Animals; D004280:Dobutamine / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D007262:Infusions, Intravenous; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D010215:Papio; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013963:Thyroid Hormones / Q000008:administration & dosage*; D016277:Ventricular Function, Left / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D013963:Thyroid Hormones; D004280:Dobutamine