Castellano M, Beschi M, Rizzoni D, Paul M, Böhm M, Mantero G, Bettoni G, Porteri E, Albertini A, Agabiti-Rosei E
Department of Internal Medicine, University of Brescia, Italy.
J Hypertens. 1993 Aug;11(8):787-91. doi: 10.1097/00004872-199308000-00004.
To study adrenergic receptors in the heart tissues of genetically hypertensive rats by evaluating the gene expression and the membrane protein density of beta 1-adrenergic receptors using steady-state messenger RNA (mRNA) levels and a radioligand binding assay, respectively.
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.
Polyadenylated RNA was extracted from individual hearts and analysed by the slot-blot technique using a beta 1-adrenergic receptor complementary DNA probe. beta-Adrenergic receptors in myocardial membranes were studied by radioligand binding assay using [125I]-cyanopindolol and the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively.
beta 1-Adrenergic receptor mRNA levels were slightly higher, and membrane protein density was similar in prehypertensive SHR and age-matched WKY rats. However, both beta 1-adrenergic receptor mRNA levels and beta 1-adrenergic receptor density were lower in the hypertensive SHR than in the control rats. beta 1-Adrenergic receptor mRNA was significantly reduced in older rats of both strains, and this reduction was most evident in the SHR.
The absence of downregulation of beta 1-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 beta 1-adrenergic receptor dysregulation. In addition, the present data suggest that the previously reported evidence of an age-related decrease in cardiac beta 1-adrenergic receptors in rats may be determined at the transcriptional level.
分别通过使用稳态信使核糖核酸（mRNA）水平和放射性配体结合试验评估β1 - 肾上腺素能受体的基因表达和膜蛋白密度，研究遗传性高血压大鼠心脏组织中的肾上腺素能受体。
我们将高血压前期（5周龄）和早期高血压（13周龄）的自发性高血压大鼠（SHR）与年龄匹配的Wistar - Kyoto（WKY）正常血压对照大鼠进行比较。
从各个心脏中提取多聚腺苷酸化RNA，并使用β1 - 肾上腺素能受体互补DNA探针通过狭缝印迹技术进行分析。心肌膜中的β - 肾上腺素能受体分别使用[125I] - 氰吲哚洛尔以及β1和β2选择性拮抗剂CGP 207.12A和ICI 118.551通过放射性配体结合试验进行研究。
高血压前期SHR和年龄匹配的WKY大鼠中，β1 - 肾上腺素能受体mRNA水平略高，膜蛋白密度相似。然而，高血压SHR中的β1 - 肾上腺素能受体mRNA水平和β1 - 肾上腺素能受体密度均低于对照大鼠。两种品系的老年大鼠中β1 - 肾上腺素能受体mRNA均显著降低，且这种降低在SHR中最为明显。
尽管已发表的数据表明SHR心脏去甲肾上腺素周转率高于WKY大鼠，但年轻SHR中β1 - 肾上腺素能受体未发生下调，这可能表明高血压前期SHR中观察到的心脏高肾上腺素能活性至少部分是由涉及β1 - 肾上腺素能受体失调的外周、突触后成分参与维持的。此外，目前的数据表明，先前报道的大鼠心脏β1 - 肾上腺素能受体随年龄下降的证据可能在转录水平上得以确定。
