速激肽受体拮抗剂对白三烯C_4引起的豚鼠心血管反应的抑制作用

INHIBTORY EFFECTS OF TACHYKININ RECCEPTOR ANTAGONISTS ON LEUK0TKIENE C4-INDUCED CARDIOVASCULAR RESPONSES IN GUINEA PIGS

ｉｖ白三烯Ｃ４（ＬＴＣ４）０．８ｎｍｏｌ·ｋｇ－１引起麻醉豚鼠血压降低和心脏微血管依文思蓝渗出增加。速激肽ＮＫ－１受体桔抗剂ＣＰ－９６３４５（２．０６ｕｍｏｌ·ｋｇ－１，ｉｖ）和ＮＫ－２受体桔抗剂ＳＲ－４８９６８（１．６６ｕｍｏｌ·ｋｇ－１，ｉｖ）部分抑制心房微血管渗漏（分别为４６．６％和３７．５％）；两药合用可明显抑制ＬＴＣ４引起的低血压和心房、心室微血管渗漏（分别为５８．１％和５４．ｌ％），其作用与白三烯特异性桔抗剂ＯＮＯ－１０７８（０．０６ｕｍｏｌ·ｋＧ－１．ｉｖ）相似。结果表明速激肽ＮＫ－１和ＮＫ－２受体可能参与白三烯引起的低血压和心脏炎症反应。

This study is to determine whether sensory neuropeptides are involved in thecardiovascular effects of leukotrieneC4(LTC4).LTC4(0. 8 nmol· kg-1,iv)caused hypotensiveresponse and increased Evans blue extravasation frOm the atria and ventricles in anaesthetized guineapigs.CP-96345(2.06umol·kg-1,iv), a tachykinin NK-1 receptor antagonist,and SR-48968(1.66umol· kg-1,iv), an NK-2 receptor antagonist,partially inhibited LTC4-induced increase(46. 6%and 37. 5%, respectively)of dye extravasation from the atria of guinea pigs. COmbination of CP-96345 and SR-48968 markedly inhibited LTC4-induced hypotension and increase of microvascularleakage in both atria and ventricles(58.1%and 54.1%, respectively),similar to the inhibition byONOI078(0. 06umol·kg-1,iv),a specific leukotriene antagonist.These resuIts suggest that NK-1and NK-2 receptors may be involved in the hypotension and the inflammation of heart induced byLTC4.