Alterations of α₁-adrenoceptor subtypes in the hearts of thyroxine-treated rats

Alterations in the cardiac α₁-adrenoceptor and its subtypes in thyroxine-treated rats were studied by means of radioligand binding assays, measurement of contractile response and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that in thyroxine-treated rats the cardiac α₁-adrenoceptor density (B_max) was reduced from 51.6 ± 6.0 fmol/mg in control to 40.9 ± 3.7 fmol/mg (P < 0.01); and the percentage of high affinity sites for 5-methyl-urapidil decreased from 23.3 ± 2.0% in control to 10.8 ± 2.0% in thyroxine-treated rats (P < 0.05). The data indicated that the high-affinity sites for 5-methyl-urapidil (α_1A-adrenoceptor) were reduced (from 12.0 to 4.4 fmol/mg), but the low-affinity sites for 5-methyl-urapidil (α_1B- plus α_1D-adrenoceptor) were not changed from 39.6 to 36.5 fmol/mg). RT-PCR showed that steady-state levels of mRNA for α_1A- and α_1B-adrenoceptors were decreased, while that for α_1D-adrenoceptor was raised in thyroxine-treated rats. In the isolated electrically driven left atria the phenylephrine-induced maximal contractions were reduced from 258 ± 17 mg in control to 188 ± 24 mg in thyroxine-treated rats (P < 0.05). The pA₂ values of 5-methyl-urapidil were reduced from 8.89 ± 0.36 in control to the hyperthyroidism of 7.87 ± 0.43 in thyroxine-treated rats (P < 0.05). Chlorethylclonidine preincubation shifted concentration-response curves for phenylephrine to the right and reduced the maximal response to a lesser extent in thyroxine-treated rats than in control rats. Thus we concluded that the total number of cardiac α₁-adrenoceptors is reduced in thyroxine-treated rats. The change is subtype selective, with α_1A- and α_1B-adrenoceptors being reduced in number and α_1D-adrenoceptor being increased.