Upregulation ofα1A-andα1B-Adrenergic Receptor mRNAs in the Heart of Cardiomyopathic Hamsters

An increased density ofα1-adrenergic receptors (AR) has been linked to the development of necrotic lesions in the heart of hamsters with hereditary cardiomyopathy. To determine whether this increase results from an upregulation of the receptor mRNA(s), Northern blot analyses were carried out in the heart of 60-day-old control and cardiomyopathic hamsters using selective DNA probes for the three subtypes ofα1-ARs (α1A,α1B, andα1D). Transcripts for the threeα1-ARs were detected in both control and cardiomyopathic hamsters. A two-fold increase in theα1A- andα1B-AR mRNA levels was observed in the cardiomyopathic hearts when compared to controls. In contrast, no change in theα1D-AR mRNA level could be detected. The enhancement inα1A- andα1B-AR mRNA levels was paralleled by a 20% increase in the total number ofα1-ARs, as assessed by [3H]prazosin radioligand binding assays. Competition binding assays using subtype selective ligands indicated that the increased density of bothα1Aandα1Breceptors contributes to the totalα1-AR upregulation. Taken together, these data suggest that the early development of hereditary cardiomyopathy in hamsters is accompanied by a specific overexpression of theα1A- andα1B-ARs. A discrete increase of theα1-AR density could contribute to eliciting coronary microspasms, therefore participating in the development of focal necrotic lesions that are characteristic of the hamster cardiomyopathic model.