GENE-EXPRESSION OF CARDIAC BETA1-ADRENERGIC RECEPTORS DURING THE DEVELOPMENT OF HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS

Objective: To study adrenergic receptors in the heart tissues of genetically hypertensive rats by evaluating the gene expression and the membrane protein density of beta1-adrenergic receptors using steady-state messenger RNA (mRNA) levels and a radioligand binding assay, respectively. Design: We compared prehypertensive (5-week-old) and early-hypertensive (13-week-old) spontaneously hypertensive rats (SHR) with age-matched Wistar-Kyoto (WKY) normotensive control rats. Methods: Polyadenylated RNA was extracted from individual hearts and analysed by the slot-blot technique using a beta1-adrenergic receptor complementary DNA probe. beta-Adrenergic receptors in myocardial membranes were studied by radioligand binding assay using [I-125]-cyanopindolol and the beta1- and beta2-selective antagonists CGP 207.12A and ICI 118.551, respectively. Results: beta1-Adrenergic receptor mRNA levels were slightly higher, and membrane protein density was similar in prehypertensive SHR and age-matched WKY rats. However, both beta1-adrenergic receptor mRNA levels and beta1-adrenergic receptor density were lower in the hypertensive SHR than in the control rats. beta1-Adrenergic receptor mRNA was significantly reduced in older rats of both strains, and this reduction was most evident in the SHR. Conclusions: The absence of downregulation of beta1-adrenergic receptors in young SHR, despite published data indicating a higher cardiac noradrenaline turnover than in WKY rats, may suggest that the cardiac hyperadrenergic activity observed in prehypertensive SHR is maintained, at least in part, by the participation of peripheral, postsynaptic component(s) involving beta1-adrenergic receptor dysregulation. In addition, the present data suggest that the previously reported evidence of an age-related decrease in cardiac beta1-adrenergic receptors in rats may be determined at the transcriptional level.