Myocardial metabolic and functional responses to acetylcholine are altered in thyroxine-induced cardiac hypertrophy

We tested the hypothesis that acetylcholine would reduce myocardial 0₂ consumption and function, and that thyroxine (T₄, 0.5 mg/kg for 16 days) induced cardiac hypertrophy would change this relationship. Anesthetized open-chest New Zealand white rabbits were divided into four groups: control-vehicle (CV, n = 8), control-acetylcholine (CA, n = 10), T₄-vehicle (T₄V, n = 9), and T₄-acetylcholine (T₄A, n = 10). Either vehicle or acetylcholine (10^-3 M) was topically applied to the left ventricular surface. Coronary blood flow (radioactive microspheres) and 0₂ extraction (microspectrophotometry) were used to determine 0₂ consumption, and muscarinic receptor density and affinity were also determined. T₄ increased the heart weight/body weight ratio from 2.6 ± 0.1 to 3.4 ± 0.1. T₄-treated animals had higher heart rates, blood pressures, and left ventricular dP/dt(max) than control rabbits. Topical acetylcholine depressed hemodynamic parameters with a greater decrement in pressures and cardiac output in the T₄A group (CA, -25%, T₄A, -40%). Myocardial O₂ consumption and coronary brood flow were higher in the T₄-treated hearts. Myocardial O₂ consumption significantly declined in both groups during acetylcholine, but the reduction was greater in the T₄-treated hearts (CV 7.9 ± 0.4 to CA 5.8 ± 0.6 and T₄V 18.8 ± 3.0 to T₄A 7.3 ± 1.0 mL 0₂·min^-1·100 g^-1). Muscarinic receptor density (B(max)) was elevated by 41% in the T₄-treated hearts, but affinity (K(d)) was not altered. Thus, the T₄-treated hearts responded to acetylcholine to a greater extent than control hearts in terms of functional and 0₂ consumption decrements. This may, in part, be related to the elevated number of muscarinic receptors in the T₄-treated rabbit hearts.