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 genet ically hypertensive rats by evaluating the gene expression and the mem brane protein density of beta1-adrenergic receptors using steady-state messenger RNA (mRNA) levels and a radioligand binding assay, respecti vely. Design: We compared prehypertensive (5-week-old) and early-hyper tensive (13-week-old) spontaneously hypertensive rats (SHR) with age-m atched Wistar-Kyoto (WKY) normotensive control rats. Methods: Polyaden ylated RNA was extracted from individual hearts and analysed by the sl ot-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, respect ively. Results: beta1-Adrenergic receptor mRNA levels were slightly hi gher, 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 hypert ensive SHR than in the control rats. beta1-Adrenergic receptor mRNA wa s significantly reduced in older rats of both strains, and this reduct ion was most evident in the SHR. Conclusions: The absence of downregul ation of beta1-adrenergic receptors in young SHR, despite published da ta indicating a higher cardiac noradrenaline turnover than in WKY rats , may suggest that the cardiac hyperadrenergic activity observed in pr ehypertensive SHR is maintained, at least in part, by the participatio n 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 be ta1-adrenergic receptors in rats may be determined at the transcriptio nal level.