Effect of clonidine on renal alpha-adrenergic receptors and development of hypertension in Dahl-Iwai salt-sensitive rats.

可乐定对 Dahl-Iwai 盐敏感大鼠肾脏 α-肾上腺素能受体和高血压发展的影响。

• 批准号: 05670625
• 负责人: FUKIYAMA Koshiro
• 金额: $ 1.47万
• 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: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670625/
• 关键词: alpha adrenergic receptor; Dahl-Iwai salt-sensitive rat; sympathetic nerve activity; kidney; clonidine treatment; Dahl-Iwai Sラット

Background : We reported that alpha2-adrenoceptor densities in Dahl-Iwai salt-sensitive (DIS) rats rats fed a high-salt diet showed lower levels in the lower brainstem and higher levels in the renal basolateral membranes and the interaction between salt and receptor regulation in the early phase of life may be essential for the development of salt-induced hypertension in DIS rats (Clin Exp Hypertens, in press). In this study, we evaluated whether clonidine inhibit the development of hypertension and clarified the effect of clonidine on alpha1-, and alpha2 adrenoceptors in renal basolateral mambranes in DIS rats.Methods : Four week-old Dahl-Iwai salt sensitive rats were divided into three groups and fed a high-salt(8.0%NaCl) until 8weeks of age. G1 : control group drunk only distillled water, G2 : clonidine group drunk only 0.4mg/L clonidine solution, G3 : withdrawal group drunk only the clonidine solution for the first 2 weeks and only distillled water for the later 2 weeks. At 8weeks … More of age, urine was collected, then renal basolateral membranes were obtained using Percoll density. Alpha1- and alpha2- adrenoceptor density were assayd using 3H-prazosin and 3H-rauwolscine. Systolic blood pressure (SBP) was measured by tail-cuff method. Urine catecholamines are assayd by HPLC.Results : At 6 weeks of age, SBPs were higher in G1 (160<plus-minus>0.8, mean<plus-minus>SEM) than G2 (144<plus-minus>0.7) and G3 (145<plus-minus>0.9). SBPs of G3 after withdrawal of clonidine rose into the same SBP levels of G1 at 8 weeks of age (G1 : 229<plus-minus>3.6, G3 : 227<plus-minus>3.6), while SBPs of G2 (198<plus-minus>0.6) were kept lower than those of G1 and G3. Urinary noradrenaline (NA) was higher in G3 (639<plus-minus>37ng/day) than G1 (441<plus-minus>38) and G2 (236<plus-minus>20). Urinary adrenaline (AD) was higher in G3 (152<plus-minus>19ng/day) than G2 (76<plus-minus>9). Both alpha1- and alpha2-adrenoceptor densities were lower in G3 (alpha1 239<plus-minus>4, alpha2 504<plus-minus>26 fmol/mg protein) than G1 (373<plus-minus>39,737<plus-minus>54) and G2(3Conclusions : (1) Clonidine treatment failed to suppress the development of hypertension in DIS.(2) Discontinuation of clonidine increased urinary catecholamine and decreased alpha1- and alpha2- adrenoceptor densities in renal basolateral membranes of DIS rats. Less

背景资料：我们报道了高盐饮食喂养的Dahl-Iwai盐敏感（DIS）大鼠的α 2-肾上腺素受体密度在下脑干中显示出较低的水平，在肾基底外侧膜中显示出较高的水平，并且在生命的早期阶段盐和受体调节之间的相互作用可能是DIS大鼠盐诱导高血压发展的关键（Clin Exp Hypertens，出版中）。方法：将4周龄Dahl-Iwai盐敏感大鼠分为3组，分别给予高盐（8.0%NaCl）喂养至8周龄，观察可乐定对DIS大鼠肾基底外侧膜α 1、α 2肾上腺素能受体的影响。第一组：对照组仅饮用纯净水，G2可乐定组仅饮用0.4mg/L可乐定溶液，G3戒断组前2周仅饮用可乐定溶液，后2周仅饮用纯净水。8周时 ...更多信息 收集尿标本，Percoll密度法获取肾基底外侧膜。用3 H-哌唑嗪和3 H-萝芙木碱测定α 1和α 2肾上腺素能受体密度。尾袖法测量收缩压（SBP）。结果：6周龄时，G1组SBP（160 ± <plus-minus>0.8，平均<plus-minus>SEM）高于G2组（144 ± <plus-minus>0.7）和G3组（145 <plus-minus>± 0.9）;停药后G3的SBP在8周龄时上升至G1的SBP水平（G1：229 <plus-minus>3.6，G3：227 <plus-minus>3.6），而G2的SBP（198 <plus-minus>0.6）保持低于G1和G3。尿去甲肾上腺素（NA）G3（639 <plus-minus>37 ng/d）高于G1（441 <plus-minus>38）和G2（236 <plus-minus>20）。尿肾上腺素（AD）G3组（152 <plus-minus>19 ng/d）高于G2组（76 <plus-minus>9）。α 1和α 2肾上腺素能受体密度在G3组（α 1 239 <plus-minus>4，α 2 504 <plus-minus>26 fmol/mg蛋白）均低于G1组（373 <plus-minus>39，737 <plus-minus>54）和G2组（3）。(2)可乐定停药增加尿儿茶酚胺和减少α 1-和α 2-肾上腺素能受体密度在DIS大鼠的肾基底外侧膜。少

项目成果

Takishita S,Muratani H,Kawazoe N,Kimura Y,Tozawa M,Fukiyama K.: "Neural effects on renal blood flow during acute hypotension vary with antihypertensive drugs." Hypertension. 23〔suoolI〕. I-97-I-101 (1994)

Takishita S、Muratani H、Kawazoe N、Kimura Y、Tozawa M、Fukiyama K.：“急性低血压期间对肾血流的神经影响因抗高血压药物而异。”23〔suoolI〕。 1994）

Tozawa M,Takishita S,Sunagawa,O,Muratani H,Imai C,Kawazoe N,Fukiyama K: "Alpha2-adrenoceptors in brain and kidney during development of hypertension in Dahl-Iwai salt-sensitive rats." Clinical and Experimental Hypertension. (in printing). (1995)

Tozawa M、Takishita S、Sunakawa、O、Muratani H、Imai C、Kawazoe N、Fukiyama K：“Dahl-Iwai 盐敏感大鼠高血压发展过程中大脑和肾脏中的 α2 肾上腺素受体。”

Tozawa M,Takishita S,Sunagawa O,Muratani H,Imai C,Kawazoe N,Fukiyama K18GB01 : Alpha2-adrenoceptors in brain and kidney during development of hypertension in Dahl-Iwai saltsensitive rats.19GC01 : Clin Exp Hypertens: (in press). (1995)

Tozawa M，Takishita S，Sunakawa O，Muratani H，Imai C，Kawazoe N，Fukiyama K18GB01：Dahl-Iwai盐敏感大鼠高血压发展过程中大脑和肾脏中的α2-肾上腺素受体。19GC01：临床实验高血压：（正在印刷中）。

Takishita S,Muratani H,Kawazoe N,Kimura Y,Tozawa M,Fukiyama K.: "Neural effects on renal blood flow during acute hypotension vary with antihypertensive drugs." Hypertension. 23[suppl I]. I-97-I-101 (1994)

Takishita S，Muratani H，Kawazoe N，Kimura Y，Tozawa M，Fukiyama K.：“急性低血压期间对肾血流的神经影响因抗高血压药物而异。”

Tozawa M,Imai C,Sunagawa O,Takishita S,Muratani H,Fukiyama K.: "Effects of high salt on brain stem and renal alpha2-adrenoreceptors in Dahl-Iwai salt-sensitive and-resistant rats.Proc 15th scientific meeting of the International Society of Hypertension,Me

Tozawa M，Imai C，Sunakawa O，Takishita S，Muratani H，Fukiyama K.：“高盐对 Dahl-Iwai 盐敏感和抗性大鼠脑干和肾 α2 肾上腺素受体的影响。Proc 第 15 届科学会议