Role of β-adrenoceptors in thyroxine-induced hypertrophy

The role of β-adrenoceptors in the development of thyroxine (T4)-induced hypertrophy was studied in New Zealand white rabbits. Radiolabelled microspheres were used to measure coronary blood flow, and (125I)-pindolol was used for Scatchard analysis of cardiac membranes to determine β-adrenoceptor density (B/sub max/) and affinity. After 16 d of T4, coronary blood flow (CBF) was elevated from 257 +/- 31 ml/min/100 g (mean +/- SD) to 530 +/- 152 and B/sub max/ increased from 24.0 +/- 6.2 fmol/mg membrane protein to 47.3 +/- 12.0. Heart weight (HW) was elevated 30%, and heart weight/body weight (HW/BW) increased 70% above control. T4 + propranolol (9 mg/kg/d) diminished CBF from levels seen with T4 alone, to 361 +/- 146 ml/min/100g. However B/sub max/ elevations were unchanged from values with T4. HW and HW/BW increases were insignificantly less than with T4 alone. CBF in T4 + pindolol (0.9 mg/kg/d) animals was similar to that with T4 alone, but B/sub max/ increases were prevented (32.0 +/- 11.0). HW and HW/BW were both lower than with T4 alone (153% of control). Thus, it appears that pindolol is more able to reverse some of the effects of T4 than is propranolol, possibly due to prevention of β-adrenoceptor upregulation as a result of its intrinsic sympathomimetic ability