Alterations of alpha1-adrenoceptor subtypes in the hearts of thyroxine-treated rats

Alterations in the cardiac alpha1-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 alpha1-adrenoceptor density (Bmax) 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 (alpha1A-adrenoceptor) were reduced (from 12.0 to 4.4 fmol/mg), but the low-affinity sites for 5-methyl-urapidil (alpha1B- plus alpha1D-adrenoceptor) were not changed (from 39.6 to 36.5 fmol/mg). RT-PCR showed that steady-state levels of mRNA for alpha1A- and alpha1B-adrenoceptors were decreased, while that for alpha1D-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 alpha1-adrenoceptors is reduced in thyroxine-treated rats. The change is subtype selective, with alpha1A- and alpha1B-adrenoceptors being reduced in number and alpha1D-adrenoceptor being increased.