Upregulation of alpha(1A)- and alpha(1B)-adrenergic receptor mRNAs in the heart of cardiomyopathic hamsters

An increased density of alpha(1)-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 of alpha(1)-ARs (alpha(1A), alpha(1B), and alpha(1D)). Transcripts for the three alpha(1)-ARs were detected in both control and cardiomyopathic hamsters. A two-fold increase in the alpha(1A)- and alpha(1B)-AR mRNA levels was observed in the cardiomyopathic hearts when compared to controls. In contrast, no change in the alpha(1D)-AR mRNA level could be detected. The enhancement in alpha(1A)- and alpha(1B)-AR mRNA levels was paralleled by a 20% increase in the total number of alpha(1)-ARs, as assessed by [H-3]prazosin radioligand binding assays. Competition binding assays using subtype selective ligands indicated that the increased density of both alpha(1A) and alpha(1B) receptors contributes to the total alpha(1)-AR upregulation. Taken together, these data suggest that the early development of hereditary cardiomyopathy in hamsters is accompanied by a specific overexpression of the alpha(1A)- and alpha(1B)-ARs. A discrete increase of the alpha(1)-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. (C) 1997 Academic Press Limited.