Effect of Isoproterenol on Coronary Blood Flow and Signal Transduction Responses in Thyroxine-treated Rabbit Hearts

This study examined the hypothesis that treatment with thyroxine (T₄) would alter the coronary blood flow and signal transduction responses of the rabbit heart. T₄ was administered for 16 days by subcutaneous time-release pellets (3 mg/kg/day) in 3 kg New Zealand white rabbits. Four groups of anesthetized open-chest rabbits (control, control + isoproterenol (ISO, 0.5 μg/kg/min for 15 min), T₄, and T₄ + ISO) were used to determine coronary blood flow (radioactive microspheres), cyclic AMP content (competitive binding), low Km cyclic-AMP-phosphodiesterase activity (cyclic AMP-PDE, conversion of³ H-cyclic AMP to³H-AMP) and β-adrenoceptor number and affinity (¹²⁵I-iodocyano-pindolol). Coronary blood flow was increased from control by ISO from 167 ± 59 to 354 ± 157 ml/min/100g. T₄ did not cause cardiac hypertrophy, but increased baseline coronary blood flow to 269 ± 115 ml/min/100g. The ISO response was attenuated in terms of blood flow (448 ± 118) and heart rate with T₄. Beta-adrenoceptor numbers increased significantly from 65.7 ± 9.2 to 81.9 ± 4.4 fmol/mg protein, while neither soluble (126 ± 39 vs 119 ± 15 pmol/mg protein/min) nor particulate cyclic AMP-PDE activity were different between control and T₄ animals. Cyclic AMP content was increased from control by both ISO (779 ± 239 to 1371 ± 672 pmol/g) and T₄ (1143 ± 244). T₄ animals showed a smaller increased in cyclic AMP following ISO (1391 ± 261). There was not a significant difference between the control and T₄ group cyclic AMP level following ISO. Thus, despite increase beta-adrenoceptor numbers, there was a diminished responsiveness of heart rate, coronary blood flow and cyclic AMP levels to isoproterenol in the T₄-treated rabbit hearts.