速激肽NK-1受体拮抗剂CP-96345对抗原诱发的豚鼠心血管反应的影响  

Effects of CP-96345, a specific tachykinin NK-1 receptor antagonist, on antigen induced cardiovascular responses in guinea pigs

作　　者：陈积愫[1] 田炯[1] 张纬萍[1] 魏尔清[1] 

机构地区：[1]浙江医科大学神经生物学实验室

出　　处：《中国药学杂志》1997年第8期469-472,共4页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金

摘　　要：目的：探讨内源性速激肽是否参与抗原诱导的豚鼠心血管反应。方法：观察速激肽ＮＫ－１受体拮抗剂ＣＰ－９６３４５对ｉｖ抗原（卵白蛋白，ＯＡ）或Ｐ物质（ＳＰ）引起致敏豚鼠血压变化及不同组织伊文思蓝渗出的影响。结果：ＯＡ（５ｍｇ·ｋｇ－１）或ＳＰ（２μｇ·ｋｇ－１）均引起麻醉豚鼠血压降低；支气管、肺内气道、心房、心室、耳廓和膀胱的伊文思蓝渗出增加。ＣＰ－９６３４５（０．３，１．０ｍｇ·ｋｇ－１，ｉｖ）不影响ＯＡ诱导的低血压反应，但可浓度依赖性抑制ＯＡ引起的支气管和肺内气道微血管渗漏；同时能阻断ＳＰ引起的低血压和各组织微血管渗漏反应。结论：抗原诱导的气道微血管渗漏反应与内源性速激肽有关。OBJECTIVE: To study whether the endogenous tachykinins are involved in the antigen induced cardiovascular responses in guinea pigs. METHOD: The effects of NK-1 receptor antagonist, CP-96345, on the changes in mean arterial pressure (MAP) and Evans blue extravasation in various tissues induced by antigen (OA) or substance P (SP) were observed in the sensitized guinea pigs. RESULTS: OA (5 mg·kg -1 , iv) and SP (2 μg·kg -1 , iv) elicited hypotensive responses, and enhanced Evans blue extravasation in the bronchi, intrapulmonary airways, atria, ventricles, ears and urinary bladders. CP-96345 (0.3 mg·kg -1 , 1 mg·kg -1 , iv), a specific NK-1 receptor antagonist did not inhibit OA induced hypotension, but dose dependently inhibited OA induced microvascular leakage in the bronchi and intrapulmonary airways. Otherwise, this compound blocked SP induced hypotension and microvascular leakage in various tissues. CONCLUSION: Endogeneous tachykinins play a role in the antigen induced airway microvascular leakage, which can selectively be inhibited by CP-96345.

关 键 词：速激肽受体 拮抗剂 CP-96345 抗原 心血管反应 

分 类 号：R974[医药卫生—药品]