Effect of thyroid status on β-adrenoceptors and calcium channels in rat cardiac and vascular tissue

Summary

To determine the influence of thyroid hormone on β-adrenoceptors and Ca²⁺ channels, rats were treated with thyroxine (75 μg/100 g sc daily for 5 days) or propylthiouracil (0.05% in drinking water for 30 days). β-Adrenoceptor density in ventricular tissue, measured by [¹²⁵I]iodocyanopindolol binding, was significantly increased and decreased respectively, following thyroxine or propylthiouracil treatment to 124.7 ± 7.11 fmol/mg protein and 71.98 ± 5.37 fmol/mg protein from euthyroid (control) levels of 93.7 ± 4.58 fmol/mg protein. Ca²⁺ channel density, measured by [³H]nitrendipine binding, was altered in the opposite direction; it was significantly decreased and increased to 324 ± 24 fmol/mg protein and 691 ± 31 fmol/mg protein from 562 ± 35 fmol/mg protein after thyroxine or propylthiouracil treatment, respectively. No changes in affinity of either ligand were observed. Responses of isolated papillary muscles from propylthiouracil-treated animals accorded with changes seen in the binding studies. The geometric mean EC₅₀ of isoproterenol increased from 9.5 × 10⁻⁹ mol/1 to 5.5 × 10⁻⁸ mol/l, and the EC₅₀ for calcium decreasedfrom 3.16 × 10⁻³ mol/1to 1.36 × 10⁻³ mol/1; moreover, the responsiveness to the Ca ²⁺ channel activator Bay K 8644 was increased. The corresponding responses in thyroxine-treated animals could not be examined because of prominent arrhythmic activity. As with papillary muscles the sensitivity of left atria to isoproterenol was decreased after treatment with propylthiouracil, with geometric mean EC₅₀ values increasing from 3.21 × 10⁻⁹ mol/1 to 89.4 × 10⁻⁹ mol/l. This was however, associated with a decrease in the sensitivity to calcium with geometric mean EC₅₀ values increasing from 2.43 × 10⁻³ mol/1 to 5.33 × 10⁻³ mol/1 and a reduction in the maximal response to Bay K 8644. Treatment with thyroxine had no effect on tissue sensitivity. The responses of isolated tail artery to phenylephrine, calcium and Bay K 8644 were not significantly different in propylthiouracil- or thyroxine-treated animals.