高血圧における末梢交感神経と血管内皮・平滑筋の相互関連に関する研究

高血压周围交感神经与血管内皮/平滑肌相互关系的研究

• 批准号: 09670735
• 负责人: HANO Takuzo
• 金额: $ 2.05万
• 依托单位: Wakayama Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670735/
• 关键词: ATP; P2x receptor; periferal sympathetic nerve; SHR; norepinephrine; 血管平滑筋; 交感神経; カルシウム; プリン受容体; アデノシン; 一酸化窒素

Aim of this study is to elucidate the contribution of ATP released from nerve ending to increased vascular tone in the pathogenesis of hypertension. Eight-week-old male Wistar rats, 8-week old male spontaneously hypertensive rats (SHR/Izm) and Wistar-Kyoto rats ( WKY/Izm) were used. Mesenteric arterial preparation was made by Castelluci's methods. Electrical stimulation was made at 0.5Hz, 5msec duration, supra-maximal voltage by platinum electrode attached the sympathetic nerves around mesenteric artery. Exogenous norepinephrine (0.25 mug) was injected to mesenteric artery to evaluate the pressor response. a, , 8-methylene-ATP (2.5x1O^<-6>M) was used as P2x receptor agonist, and suramin (10^<-5>M) was used as P2 antagonist. 0.5Hz of electrical stimulation has no effects on perfusion pressure. 0.5 Hz of electrical stimulation increased norepmephrine-induced pressor response by 162.3% compared with pre-stimulated condition. Blood pressure and body weight of SHR/Izm and WKY/Izm were 174.2mmHg, 139g, 139.OmmHg, 147g, respectively. Pub-pressor frequency of electrical stimulation has no effects on pressor response to norepinephrine in both of SHR/Izm and WKY/Izm. alpha, beta -methylene-ATP increased pressor response to norepinephrine by 128.2% in SHR/Izm, by48.9% in WKY/Izm. ATP released from nerve ending augment the pressor response to norepinephrine through the P2x receptors. In SHR/Izm and WKY/Izm shows no augmented effects of electrical stimulation on pressor response, in contrast, alpha, beta -methylene-ATP has augmented effects on it. These results shows reduced co-release of ATP in SHR/Izm and WKY/Izm.

这项研究的目的是阐明在高血压发病机理中从神经结尾释放到增加血管张力的ATP的贡献。使用了八周大的雄性Wistar大鼠，8周的雄性自发性高血压大鼠（SHR/IZM）和Wistar-Kyoto大鼠（WKY/IZM）。肠系膜动脉制剂是通过Castelluci的方法进行的。电刺激在0.5Hz，5msec持续时间，铂电极上的超Xima刺激电压附着在肠系膜动脉周围附着交感神经。将外源性去甲肾上腺素（0.25杯）注射到肠系膜动脉中，以评估压力反应。 A，8-甲基-ATP（2.5x1O^<-6> m）用作P2X受体激动剂，Suramin（10^<-5> m）用作P2拮抗剂。 0.5Hz的电刺激对灌注压力没有影响。与预刺激的条件相比，0.5 Hz的电刺激增加了去甲肾上腺素诱导的压力反应的162.3％。 SHR/IZM和WKY/IZM的血压和体重分别为174.2mmHg，139g，139.ommhg，147g。在SHR/IZM和WKY/IZM中，Pub-Press-pressor的电刺激频率对压压反应没有影响。 Alpha，β-甲基-ATP在SHR/IZM中增加对去甲肾上腺素的压力反应增加了128.2％，WKY/IZM中的压压反应增加了48.9％。 ATP从神经末端释放出来，通过P2X受体对去甲肾上腺素的压力反应。相反，在SHR/IZM和WKY/IZM中，电刺激对压力响应的影响没有增强的影响，相反，α，β-甲基-ATP对其进行了增强的影响。这些结果表明，在SHR/IZM和WKY/IZM中，ATP的共释放减少了。

项目成果

Imanishi et al: "Effects of locally administered argatroban on restenosis after ballon angioplasty : experimental and clinical study" Clin Exp Pharmacol Physiol. 24. 800-806 (1997)

Imanishi 等人：“局部施用阿加曲班对球囊血管成形术后再狭窄的影响：实验和临床研究”Clin Exp Pharmacol Physiol。

Mizukoshi M et al: "Abnormal regulation angiotensin II receptor type 1 gene expression in th adrenal gland of spontaneously hypertesive rats" Japanese Heart Journal. 78(4). 32 (1997)

Mizukoshi M等人：“自发性高血压大鼠肾上腺中血管紧张素II受体1型基因表达的异常调节”日本心脏杂志。

Yoshikawa H et al.: "Enhanced efficacy of nilvadipine in hypertensives whose raised ambulatory blood pressure is sustained during sleep." American Journal of Hypertension.11(1 Pt 1). 122-124 (1998)

Yoshikawa H 等人：“对于睡眠期间动态血压持续升高的高血压患者，尼伐地平的疗效增强。”

Imanishi T et al.: "Effects of locally administered argatroban on restenosis after balloon angioplasty:experimental and clinical study" Clin Exp Pharmacol Physiol. 24. 800-806 (1997)

Imanishi T 等人：“局部施用阿加曲班对球囊血管成形术后再狭窄的影响：实验和临床研究”Clin Exp Pharmacol Physiol。

Imanishi T et al.: "Effects of locally administered argatroban on restenosis after balloon angioplasty : experimental and clinical study" Clin Exp Pharmacol Physiol. 24. 800-806 (1997)

Imanishi T 等人：“局部施用阿加曲班对球囊血管成形术后再狭窄的影响：实验和临床研究”Clin Exp Pharmacol Physiol。