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

本研究旨在阐明神经末梢释放的三磷酸腺苷在高血压发病机制中对血管张力增加的作用。选用8周龄雄性Wistar大鼠、8周龄雄性自发性高血压大鼠(SHR/IZM)和Wistar-京都大鼠(WKY/IZM)。按Castelluci方法制备肠系膜动脉。电刺激频率0.5 Hz，持续时间5ms，超最大电压，用铂电极连接肠系膜动脉周围的交感神经。肠系膜动脉注射外源性去甲肾上腺素(0.25µg)以评价升压反应。P2受体激动剂为α，8-亚甲基-三磷酸腺苷(2.5x10；-6&gt；M)，P2拮抗剂为苏拉明(10^&lt；-5&gt；M)。0.5赫兹的电刺激对灌流压无影响。与刺激前相比，162.3.5Hz电刺激使去甲肾上腺素引起的升压反应增加1%。SHR/IZM和WKY/IZM的血压和体重分别为174.2 mm Hg、139 g、139 mm Hg、147 g。SHR/IZM和WKY/IZM的耻骨升压频率对去甲肾上腺素的升压反应均无影响。α，β-亚甲基-三磷酸腺苷使SHR/IZM对去甲肾上腺素的升压反应增加128.2%，WKY/IZM增加48.9%。神经末梢释放的三磷酸腺苷通过P2x受体增强去甲肾上腺素的升压反应。在SHR/IZM和WKY/IZM中，电刺激对升压反应没有增强作用，相反，α，β-亚甲基-ATP对升压反应有增强作用。这些结果表明，SHR/IZM和WKY/IZM的ATP共释放减少。

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.