[en] 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

[en] The purpose of this study was to investigate the hypothesis that the heterogeneous distribution of β adrenoceptors contributes to the control of flow heterogeneity in the canine myocardium. β adrenoceptor density and affinity were measured simultaneously with coronary blood flow in multiple sections of the left ventricle of 14 anesthetized open chest dogs. Radioactive microspheres were used for the measurement of blood flow. Receptor density (Bmax) and dissociation constant (Kd) were measured using [¹²⁵I]- iodopindolol. The average control myocardial blood flow (MBF) was 86/+-/15 ml/min/100 g. Isoproterenol increased MBF by 82%, whereas propranolol reduced MBF by 13%. The mean value of Bmax was unaltered by either treatment. Under control conditions, a significant positive positive correlation was observed between Bmax and blood flow. In the isoproterenol treatment group, this correlation was enhanced. Beta adrenoceptor blockade led to a negative correlation. Kd showed no overall correlation with blood flow. Kd but not Bmax was significantly higher in the EPI than in the ENDO and in the base compared to the apex. There appears to be a direct linear relationship between the distribution of beta adrenoceptors and MBF distribution which is enhanced under conditions of high beta adrenergic activity. There is a correlation between beta adrenoceptor activity and blood flow distribution in the canine myocardium

[en] The ability of beta-adrenoceptor blockade to reduce the hypertrophic response to thyroxine (T4, 0.5 mg/kg per day, s.c.) was tested in New Zealand white rabbits. Two beta-adrenergic blocking agents, one a full antagonist (propranolol, 9.6 mg/kg per day) and the other a partial agonist (pindolol, 0.96 mg/kg per day) were administered in combination with T4 in an effort to reduce myocardial hypertrophy. A 3 and 16 day group were generated to test the time course of the hypertrophic and receptor responses. Coronary blood flow was measured using radioactive microspheres, and beta-adrenoceptor number and affinity were measured using 125I(-) pindolol as the radioligand. T4 increased coronary blood flow to 1.95 times control values in the 3 day group and 2.2 times control levels in the 16 day group; beta-adrenoceptor number was increased similarly in 3 and 16 day groups to 1.9 times control Bmax levels. Heart weight (HW) to body weight (BW) ratios were significantly increased in only the 16 day group to 1.22 and 1.61 times control, respectively. Treatment with propranolol + T4 blunted the coronary blood flow increase, but receptor upregulation occurred to the same extent as with either substance alone. The HW/BW was increased to 1.49 times control. Pindolol + T4 did not decrease coronary blood flow but blocked beta-adrenoceptor upregulation. The HW was reduced to control levels and the HW/BW ratio was 1.40 times control and significantly decreased from T4 alone. Thus, pindolol was effective in reducing the hypertrophic response to T4, whereas propranolol was only moderately effective in doing so