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 of 3 H-cyclic AMP to 3H-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.