Canessa L M, Piccio M M, Vachvanichsanong P, Sidhu A, Porter C C, Robillard J E, Felder R A, Jose P A
Department of Pediatrics, Georgetown University Children's Medical Center, Washington, D.C., USA.
Kidney Int. 1995 Nov;48(5):1412-9. doi: 10.1038/ki.1995.430.
Although several alpha-adrenergic receptor genes are expressed in the rat kidney, their expression in the renal vasculature has not been studied. Since pharmacological studies have suggested that an alpha 1B-adrenergic receptor may mediate renal vasoconstriction, we studied the expression of alpha 1B-adrenergic receptors in renal microvessels, from 10- to 14-week-old male spontaneously hypertensive rats (SHR) and their normotensive control, the Wistar-Kyoto rat (WKY). In these microvessels, isolated by perfusion with iron, alpha 1B-adrenergic receptor mRNA levels (by ribonuclease protection assay) were similar in SHR and WKY rats. Photo-affinity labeling with [125I]-arylazidoprazosin demonstrated the presence of alpha 1B-adrenergic receptor protein. Maximum receptor density (determined by 3H-prazosin binding: Bmax 59.8 +/- 4.1 and 58.7 +/- 4.3; Kd 0.48 +/- 0.05 nM and 0.31 +/- 0.06 nM in SHR and WKY, respectively) and chloroethylclonidine (CEC)-sensitive binding sites (determined by [125I]-(2-beta(4-hydroxyphenyl)-ethylaminomethyl)-tetralone binding) (125I-HEAT) were similar in SHR and WKY rats. There are two novel findings in these studies: (1) the alpha 1B-adrenergic receptor gene is expressed in renal microvessels of WKY and SHR; (2) alpha 1B-adrenergic receptor gene expression in renal microvessels is not altered in adult SHR. The failure to down-regulate expression of the alpha 1B-adrenergic receptor at the mRNA and protein level in the SHR could result in persistence of alpha 1B-adrenergic receptor effects and contribute to the increased vascular resistance in hypertension.
尽管大鼠肾脏中表达了几种α-肾上腺素能受体基因，但它们在肾血管系统中的表达尚未得到研究。由于药理学研究表明α1B-肾上腺素能受体可能介导肾血管收缩，我们研究了10至14周龄雄性自发性高血压大鼠（SHR）及其血压正常对照Wistar-Kyoto大鼠（WKY）肾微血管中α1B-肾上腺素能受体的表达。在用铁灌注分离的这些微血管中，SHR和WKY大鼠的α1B-肾上腺素能受体mRNA水平（通过核糖核酸酶保护试验）相似。用[125I]-芳基叠氮哌唑嗪进行光亲和标记证明了α1B-肾上腺素能受体蛋白的存在。最大受体密度（通过3H-哌唑嗪结合测定：SHR和WKY中的Bmax分别为59.8±4.1和58.7±4.3；Kd分别为0.48±0.05 nM和0.31±0.06 nM）以及氯乙可乐定（CEC）敏感结合位点（通过[125I]-(2-β(4-羟基苯基)-乙基氨基甲基)-四氢萘酮结合测定）（125I-HEAT）在SHR和WKY大鼠中相似。这些研究中有两个新发现：（1）α1B-肾上腺素能受体基因在WKY和SHR的肾微血管中表达；（2）成年SHR肾微血管中α1B-肾上腺素能受体基因表达未改变。SHR中未能在mRNA和蛋白质水平下调α1B-肾上腺素能受体的表达可能导致α1B-肾上腺素能受体效应持续存在，并导致高血压中血管阻力增加。
