Central and renal alpha-adrenergic receptor with the development of salt-induced hypertension in Dahl-Iwai salt-sensitive rats.

中枢和肾脏 α-肾上腺素能受体与 Dahl-Iwai 盐敏感大鼠中盐诱导高血压的发展。

• 批准号: 03670461
• 负责人: FUKIYAMA Koshiro
• 金额: $ 1.28万
• 依托单位: University of The Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670461/
• 关键词: alpha adrenergic receptor; Dahl-Iwai S rat; sympathetic nerve; salt-induced hypertension; brain; CVLM; kidney; 腎交感神経

We reported altered alpha2-adrenoceptors in renal basolateral membrane and alphal-and alpha2 adrenoceptors in spontaneously hypertensive rats fed a low salt diet(J Hypertension 9 : 901-908, 1991, Ryukyu Medical J 12 : 62-73, 1991). In this study, we evaluated the number and affinity of alpha-adrenoceptors of brain and kidney with the development of hypertension in Dahl-Iwai salt-sensitive (Dahl-Iwai S) rats which are an experimental animal model of salt-induced hypertension. And in order to investigate extensively whether alpha-adrenoceptors in medulla oblongata were involved in salt-induced hypertension of Dahl-Iwai salt-sensitive rat, we studied effect of microinjection of alpha-agonist and alpha-antagonist into the cardiovascular center by measuring blood pressure and pulse.Receptor binding study : Dahl-Iwai S rats were fed on high(8.0%)- or low(0.3%)-salt diet for 2 or 6 weeks from 4 weeks of age. At the age of 6 or 10 weeks, we measured sodium balance and quantified alphal- and al … More pha2-adrenergic receptors of brain and renal tubular basolateral membranes by radioligand binding assay. At the age of 6 weeks, alpha2-receptor densities in medulla oblongata was lower and alphal- and alpha2-receptors densities on the renal basolateral membrane were higher in the high-salt group than in the low salt group. The difference between the groups disappeared at the age of 10 weeks. Rats fed on high-salt group showed more positive sodium balance at the age of 6 weeks (+0.06mEq/day/g body weight) compared to the age of 10 weeks (+0.02mEq/day/g body weight). Through a decrease in the alpha2-receptor in the medulla oblongata and an increase in alphal-and alpha2 receptors in the renal tubular basolateral membrane, high salt intake may result in enhancement of the sympathetic nerve activity and sodium retention. These mechanisms may contribute to the development of hypertension in Dahl-Iwai salt-sensitive rats.Experiment of microinjection : Dahl-Iwai rats were fed on high(8.0%)- or low(0.3%)-salt diet for 10-14 days from 6weeks of age, and anesthetized with urethane. Microinjection of clonidine (alpha2- agonist) into the rostral ventro lateral medulla (RVLM) decreased blood pressure(BP) and pulse rate in Dahl S and R rats either on low- and high-salt diet. Injection of SK&F86466 (alpha2-antagonist), however, did not change BP and pulse rate. In contrast, injection of clonidine into the caudal ventrolateral medulla (CVLM) caused a persistant BP elevation which was sometimes followed by a transient fall in BP. And injection of SK&F86466 into CVLM caused a depressor effect. Thus, intrinsic mechanisms involving in alpha2-adrenoceptor tonically inhibited the local cardiovascular neuron in CVLM. Less

我们报道了在喂食低盐饮食的自发性高血压大鼠中改变的肾基底外侧膜中的α 2肾上腺素受体和肾α 1和α 2肾上腺素受体（J Hypertension 9：901-908，1991，Ryukyu Medical J 12：62-73，1991）。在本研究中，我们评估了在Dahl-Iwai盐敏感（Dahl-Iwai S）大鼠，这是一种实验性盐诱导的高血压动物模型的脑和肾的α-肾上腺素受体的数量和亲和力与高血压的发展。为了深入研究延髓α-肾上腺素能受体是否参与了盐敏感性大鼠的盐性高血压，我们通过测量血压和脉搏，研究了向心血管中枢微量注射α-激动剂和α-拮抗剂的效应。受体结合研究：Dahl-Iwai S大鼠从4周龄开始喂高盐（8.0%）或低盐（0.3%）饮食2或6周。在6或10周龄时，我们测量了钠平衡，并定量了钠和铝的含量。 ...更多信息 放射性配体结合试验测定脑和肾小管基底外侧膜的α 2肾上腺素能受体。6周龄时，高盐组大鼠延髓α 2受体密度较低，肾基底外侧膜α 2和α 2受体密度高于低盐组。两组之间的差异在10周龄时消失。高盐组大鼠在6周龄时（+0.06mEq/天/g体重）比10周龄时（+0.02mEq/天/g体重）表现出更多的正钠平衡。通过延髓中α 2受体的减少和肾小管基底外侧膜中α 1和α 2受体的增加，高盐摄入可导致交感神经活性和钠潴留的增强。微量注射实验：Dahl-Iwai大鼠从6周龄起分别给予高盐（8.0%）或低盐（0.3%）饮食10-14天，乌拉坦麻醉。在Dahl S和R大鼠的头端延髓腹外侧（RVLM）微量注射可乐定（α 2-激动剂），无论是低盐饮食还是高盐饮食，都能降低血压（BP）和脉率。然而，注射SK&F86466（α 2-拮抗剂）并不改变BP和脉率。相反，注射可乐定到尾侧延髓腹外侧（CVLM）引起持续的血压升高，有时随后血压短暂下降。CVLM内注射SK&F86466可引起降压作用。因此，涉及α 2-肾上腺素受体的内在机制紧张性抑制CVLM中的局部心血管神经元。少

项目成果

Tozawa M, Sunagawa O,Kawazoe N,Takishita S,Muratani H,Fukiyama K: "A concomitant change in central and renal alpha-adrenoerceptors with the development of hypertension in Dahl-Iwai salt-sensitive rats" Journal of Hypertension. 10. S67- (1992)

Tozawa M、Sunakawa O、Kawazoe N、Takishita S、Muratani H、Fukiyama K：“Dahl-Iwai 盐敏感大鼠高血压发生时中枢和肾脏 α 肾上腺素受体的伴随变化”高血压杂志。

Sunagawa O,Fukiyama K,Noda Y,Kimura Y, Eto T: "Low-sodium diet and α-adrenoceptors of renal basolateral membrane in spontaneously hypertensive rats." Journal of Hypertension. 9. 901-908 (1991)

Sunakawa O、Fukiyama K、Noda Y、Kimura Y、Eto T：“自发性高血压大鼠的低钠饮食和肾基底外侧膜的 α-肾上腺素受体。” 高血压杂志 9. 901-908 (1991)。

戸澤 雅彦,砂川 長彦,瀧下 修一,柊山 幸志郎: "食塩負荷によるDahlSラットの腎および脳内α受容体の変化" 高血圧. 14. 25- (1991)

Masahiko Tozawa、Nagahiko Sunakawa、Shuichi Takishita、Koshiro Hiragiyama：“盐负荷导致 DahlS 大鼠肾和脑 α 受体的变化”高血压。

Sunagawa O,Fukiyama K,Noda Y,Kimura Y,Eto T: "Lowーsodium diet and αーadrenoceptors of renal basolateral membrane in spontaneously hypertensive rats." Journal of Hypertension. 9. 901-908 (1991)

Sunakawa O、Fukiyama K、Noda Y、Kimura Y、Eto T：“自发性高血压大鼠的低钠饮食和肾基底外侧膜的 α-肾上腺素受体。” 高血压杂志 9. 901-908 (1991)。

Tozawa M,Sunagawa O,Kawazoe N,Takishita S,Muratani H,Fukiyama K: "A concomitant change in central and renal alpha-adrenoreceptors with the development of hypertension in Dahl-Iwai salt-sensitive rats" Journal of Hypertension. 10. S67- (1992)

Tozawa M、Sunakawa O、Kawazoe N、Takishita S、Muratani H、Fukiyama K：“Dahl-Iwai 盐敏感大鼠高血压发生时中枢和肾脏 α 肾上腺素受体的伴随变化”高血压杂志。