Myocardial metabolic and functional responses to acetylcholine are altered in thyroxine-induced cardiac hypertrophy.
We tested the hypothesis that acetylcholine would reduce myocardial O2 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 O2 extraction (microspectrophotometry) were used to determine O2 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/dtmax 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 blood 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 O2.min-1.100 g-1). Muscarinic receptor density (Bmax) was elevated by 41% in the T4-treated hearts, but affinity (Kd) was not altered. Thus, the T4-treated hearts responded to acetylcholine to a greater extent than control hearts in terms of functional and O2 consumption decrements.(ABSTRACT TRUNCATED AT 250 WORDS)
Weiss
H R
HR
Department of Physiology and Biophysics, Piscataway 08854-5635, USA.
Tse
J
J
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced*; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013974:Thyroxine / Q000494:pharmacology*
D011976:Receptors, Muscarinic; D000109:Acetylcholine; D013974:Thyroxine