Alterations of cardiac alpha 1-adrenoceptor subtypes in hypothyroid rats.
1. Alterations in the cardiac alpha 1-adrenoceptor and its subtypes in hypothyroid rats were studied by radioligand binding assays and reverse transcription-polymerase chain reaction (RT-PCR). Hypothyroidism was created by feeding rats with 0.2% 2-thiouracil solution instead of daily drinking water for 20 days. 2. The density of cardiac alpha 1-adrenoceptors (Bmax) was increased from 67.5 +/- 4.3 fmol/mg in control rats to 81.1 +/- 7.2 fmol/mg (P < 0.05) in hypothyroid rats. 3. Compared with control rats, in hypothyroid rats the percentages of high-affinity sites for (+)-niguldipine and 5-methylurapidil were increased from 13.8 +/- 5.6 and 31.9 +/- 6.3%, respectively, to 24.9 +/- 7.3 and 45.5 +/- 2.4%, respectively (both P < 0.05), while those for BMY7378 were decreased from 37.2 +/- 8.9 to 23.8 +/- 8.4% (P < 0.05), respectively. The percentage of high-affinity sites for WB4101 was not significantly different in control and hypothyroid rats (43.3 +/- 9.1 and 39.4 +/- 3.6%, respectively). 4. Reverse transcription-PCR experiments revealed that the steady state levels of mRNA for alpha 1A- and alpha 1B-adrenoceptors were increased, while those for alpha 1D-adrenoceptor were decreased in the hearts of hypothyroid rats. 5. The concentration-contraction response curves for noradrenaline in the presence of a beta-adrenoceptor antagonist in control and hypothyroid rats showed that the maximal response was reduced from 344 +/- 58 to 200 +/- 23 mg, respectively (P < 0.05). 6. The data suggest that in hypothyroid rats the total number of cardiac alpha 1-adrenoceptors is increased. The change is subtype-selective, with levels of alpha 1A- and alpha 1B-adrenoceptors being increased and levels of alpha 1D-adrenoceptors being reduced. Furthermore, the positive inotropic response mediated by alpha 1-adrenoceptors is reduced in hypothyroid rats.
Zhang
Y
Y
Institute of Vascular Medicine, Third Hospital, Beijing Medical University, China.
Xu
K
K
Han
C
C
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D001667:Binding, Competitive / Q000187:drug effects; D017931:DNA Primers; D004095:Dihydropyridines / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010627:Phenethylamines / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D044024:Tetralones; D013889:Thiouracil
D000317:Adrenergic alpha-Antagonists; D017931:DNA Primers; D004095:Dihydropyridines; D004146:Dioxanes; D010627:Phenethylamines; D010879:Piperazines; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D044024:Tetralones; C057446:5-methylurapidil; C010652:BE 2254; D013889:Thiouracil; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; C053428:BMY 7378; D009638:Norepinephrine; C054074:niguldipine