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Central roles of GABA,glutamic acid decarboxylase (GAD) activity and mRNA GAD expression in the regulation of blood pressured and vasopressin release in sportaneous hypertensive rats (SHR)

GABA、谷氨酸脱羧酶 (GAD) 活性和 mRNA GAD 表达在运动性高血压大鼠 (SHR) 血压和加压素释放调节中的核心作用

基本信息

批准号：
07457162
负责人：
KIMURA Tokihisa
金额：
$ 4.48万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457162/
关键词：
GABA Glutamate GAD Vasopressin Hypertension Brain Amino acid microdialysis Vasopressin mocrodialysis バゾプレシン微小透析法 SHR

项目摘要

It is known that central amino acid (AA) plays important roles in the regulation of blood pressure and hormonal release. GABA suppresses a neural activity and glutamate (GLU) activates it. Thus, it is likely that the distortion of these AA release may affect the central regulation of blood pressure (BP) and vasopressin (AVP) release, thereby leading to hypertension.In the present study, in order to investigate central roles of AA in the development of hypertension in SHR,GABA and GLU release adjacent to the paraventricular nucleus were determined using a microdialysis method under osmotic and hemorrhagic stimuli in conscious SHR and normotensive rats (WKY), and BP and AVP release were also determined. Moreover, central changes in a glutamic acid decarboxylase (GAD) activity and GAD mRNA expression were determined in SHR and WKY.In intravenous administration of 2.5M NaCl, increases in plasma AVP levels and BP in SHR were greater than their increases in WKY,but central GABA release in SHR was smaller than it in WKY.GLU decreased in SHR and WKY.In hemorrhagic decreases in BP to the same extent, plasma AVP in SHR increased greater than it in WKY,but GABA and GLU decreased. There were no differences in them in SHR and WKY.A GAD activity and mRNA GAD expression in 11 week-old SHR were smaller than them in 11 week-old WKY.In conclusion, decreases in a GAD activity, its expression and GABA release might be related to the development of hypertension and enhanced AVP release in SHR.

众所周知，中心氨基酸（AA）在血压调节和激素释放中发挥着重要作用。 GABA 抑制神经活动，而谷氨酸 (GLU) 则激活神经活动。因此，这些AA释放的扭曲很可能会影响血压（BP）和加压素（AVP）释放的中枢调节，从而导致高血压。在本研究中，为了探讨AA在SHR高血压发生中的核心作用，采用微透析法测定了清醒状态下渗透性和出血性刺激下室旁核附近的GABA和GLU释放。还测定了 SHR 和正常血压大鼠 (WKY) 以及 BP 和 AVP 释放。此外，在SHR和WKY中测定了谷氨酸脱羧酶（GAD）活性和GAD mRNA表达的中心变化。静脉注射2.5M NaCl时，SHR中血浆AVP水平和血压的增加大于WKY中的增加，但SHR中中心GABA的释放小于WKY中的。SHR和WKY中GLU减少。在出血性血压降低相同程度时， SHR组血浆AVP较WKY组升高幅度更大，但GABA和GLU降低。 SHR和WKY之间没有差异。11周龄SHR的GAD活性和mRNA GAD表达量均小于11周龄WKY。综上所述，GAD活性及其表达和GABA释放的降低可能与SHR高血压的发生和AVP释放增加有关。