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

 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，CP－96345对此有选择性抑制作用。

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

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.