Le Jossec M, Cloix J F, Dausse J P
Service de biochimie de Paris-Ouest, UFR biomédicale des Saints-Pères, Paris.
Arch Mal Coeur Vaiss. 1995 Aug;88(8):1229-32.
alpha 2-adrenoceptors are involved in various renal functions regulating blood pressure. They were classified in subtypes whom genes were identified in both humans and rats. In rat renal cortex it was evidenced that the alpha 2B isoform is predominant. This result was confirmed in Sabra rats. However, the renal cortex alpha 2B density is higher in salt-sensitive (SBH) than in salt-resistant (SBN) Sabra rats. alpha 2B-adrenoceptors were recently subclassified in two pharmacologically distinct subtypes exhibiting high and low affinity for guanoxabenz and respectively called alpha 2B1 and alpha 2B2. We studied sodium loading effect on alpha 2B1 and alpha 2B2 distribution in Sabra rat renal cortex using competition experiments between [3H]-yohimbine and guanoxabenz. The rats were submitted to normal (0.2%) or high sodium diet (8%) for six weeks. Under normal diet, proportion alpha 2B1 and alpha 2B2 was similar in SBH and SBN. Nevertheless, their respective densities were significantly higher in SBH as compared to SBN (alpha 2B1: 90.6 +/- 4.1 vs 57.4 +/- 2.5 fmoles/mg prot, p < 0.0001; n = 5; alpha 2B2: 102.7 +/- 4.0 vs 66.4 +/- 4.6 fmoles/mg prot; p < 0.0001; n = 5). Under high sodium diet the distribution of these two isoforms was altered. The densities of alpha 2B1 were decreased by 27.0 +/- 5.9% in SBH (68.0 +/- 4.0 fmoles/mg prot; p < 0.0001, n = 5) and by 47.3 +/- 7.4% for SBN (29.2 +/- 3.1 fmoles/mg prot; p < 0.0001; n = 5). Conversely, the densities of alpha 2B2 were increased by 28.3 +/- 5.4% in SBH (131.1 +/- 9.5 fmoles/mg prot; p < 0.001; n = 5) and by 75.0 +/- 17% in SBN (123.2 +/- 9.1 fmoles/mg prot; p < 0.0001; n = 5). In conclusion, alpha 2B1- and alpha 2B2-adrenoceptor subtypes are found in renal cortex of both SBH and SBN. Our data demonstrated an equal distribution of these two isoforms between SBH and SBN under normal salt diet. This distribution is largely altered, especially in SBN, by the high sodium diet. From these modifications might result differential renal responses to activation of alpha 2B-adrenoceptors between SBH and SBN, and consequently responsible for normal or high blood pressure after high sodium diet.
α2 - 肾上腺素能受体参与调节血压的多种肾脏功能。它们被分为不同亚型,其基因在人类和大鼠中均已被鉴定。在大鼠肾皮质中,已证实α2B亚型占主导。这一结果在Sabra大鼠中得到了证实。然而,盐敏感型(SBH)Sabra大鼠肾皮质中的α2B密度高于盐抵抗型(SBN)Sabra大鼠。α2B - 肾上腺素能受体最近被进一步细分为两种药理学上不同的亚型,它们对胍那苄表现出高亲和力和低亲和力,分别称为α2B1和α2B2。我们使用[3H] - 育亨宾和胍那苄之间的竞争实验,研究了钠负荷对Sabra大鼠肾皮质中α2B1和α2B2分布的影响。将大鼠给予正常(0.2%)或高钠饮食(8%)六周。在正常饮食条件下,SBH和SBN中α2B1和α2B2的比例相似。然而,与SBN相比,它们各自的密度在SBH中显著更高(α2B1:90.6±4.1对57.4±2.5飞摩尔/毫克蛋白,p < 0.0001;n = 5;α2B2:102.7±4.0对66.4±4.6飞摩尔/毫克蛋白;p < 0.0001;n = 5)。在高钠饮食条件下,这两种亚型的分布发生了改变。α2B1的密度在SBH中降低了27.0±5.9%(68.0±4.0飞摩尔/毫克蛋白;p < 0.0001,n = 5),在SBN中降低了47.3±7.4%(29.2±3.1飞摩尔/毫克蛋白;p < 0.0001;n = 5)。相反,α2B2的密度在SBH中增加了28.3±5.4%(131.1±9.5飞摩尔/毫克蛋白;p < 0.001;n = 5),在SBN中增加了75.0±17%(123.2±9.1飞摩尔/毫克蛋白;p < 0.0001;n = 5)。总之,在SBH和SBN的肾皮质中均发现了α2B1和α2B2 - 肾上腺素能受体亚型。我们的数据表明,在正常盐饮食条件下,这两种亚型在SBH和SBN之间分布均匀。这种分布在很大程度上被改变了,尤其是在SBN中,高钠饮食导致了这种改变。这些变化可能导致SBH和SBN对α2B - 肾上腺素能受体激活的肾脏反应不同,从而导致高钠饮食后血压正常或升高。