異丁香醇衍生物對於大鼠心血管作用之研究

The Cardiovascular Study of Isoeugenol Derivative in the Rat

沈國屏(Kuo-Ping Shen) ； 梁至中(Jyh-Chong Liang)

《幼兒保育學刊》 4期 (2006/12) Pp. 243-258

https://doi.org/10.6433/JCC.200612.0243

摘要

臨床上常使用交感神經阻斷劑做為高血壓的治療藥物，但最近幾年許多降血壓藥物以同時具備交感神經阻斷及阻斷作用，讓病患有更多、更好的藥物來選擇，而這類藥物在治療心血管疾病上，也能發揮出比以往交感神經阻斷劑更好的療效。本科室目前已合成出一系列以異丁香醇(isoeugenol)為主幹並結合不同官能基的化合物，利用交感神經、接受體(、-adrenoceptor)阻斷及抗氧化等多方面機轉來治療心血管疾病，本研究便是以異丁香醇為基礎，結合chloro-piperazinyl benzene(CPB)、aryloxypropanolamine 之新化合物eugenosedin-A，評估其在血清素接受體(serotonin receptor)及、-adrenoceptor阻斷之活性，並針對正常血壓大鼠(Wistar-Kyoto rat; WKY)和自發性高血壓大鼠(spontaneously hypertensive rat; SHR)探討eugenosedin-A造成之血壓、血管及心房張力變化，並利用這兩種不同品系大鼠的組織進行接受體結合實驗來比較eugenosedin-A在彼此間的差異。實驗結果：在監測血壓心跳實驗中可以發現，eugenosedin-A(1.0、3.0、5.0、10.0 mg/kg)經由靜脈注射於pentobarbital麻醉之WKY及SHR，可引起心跳減緩及持續性血壓下降反應。另外，eugenosedin-A亦具有抑制5-HT2A、1、2及1接受體之活性。基於以上研究結果證實eugenosedin-A透過抑制交感神經及血清素接受體的作用機轉，降低WKY及SHR的血壓心跳、減少血管和心臟張力，這樣的作用也比目前臨床上所使用的藥物效果更好，讓我們有信心繼續往後的研究。

關鍵字

交感神經 ； 血清素 ； 高血壓

並列摘要

Eugenosedin-A is a newly synthesized compound especially with serotonergic, α- and β1-adrenergic blocking actions. Intravenous injection of eugenosedin-A significantly caused dose-dependent decreases the mean arterial blood pressure and heart rate in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). The effects of eugenosedin-A decreased blood pressure and heart rate in SHR were more potent than in WKY. In in vitro experiments, eugenosedin-A competitively antagonized the serotonin-, norepinephrine-, clonidine- and UK14304-induced vasocontraction in a concentration-dependent manner in isolated thoracic aorta of WKY and SHR. We also observed that eugenosedin-A competitively antagonized the isoproterenol-induced positive inotropic effects in a concentration-dependent manner in isolated left atrium of WKY and SHR. These findings clearly suggested that eugenosedin-A possesses α1/α2, β1, and 5-HT(subscript 2A) receptor blocking activities. Finally, we suggested that the hypotensive effects of eugenosedin-A attributed to its multiple actions on the blockade of 5-HT(subscript 1B), 5-HT(subscript 2A), α andβ1 receptors in both WKY and SHR strains.

並列關鍵字

adrenoceptors ； serotonin receptors ； hypertension