缓激肽引起的内皮源性超极化因子在调节冠状动脉阻力血管张力中的作用

Bradykinin-elicited hyperpolarizing factor contributes to vasodilation of coronary microcirculation

本研究用离体兔心灌注模型比较内皮源性超极化因子（ＥＤＨＦ）与内皮源性舒张因子（Ｅ－ＤＲＦ即一氧化氮）和前列环素（ＰＧＩ２）的特性。（１）注人缓激肽（Ｂｋ３～３０００ｐｍｏｌ／Ｌ）产生剂量依赖性扩张反应，以冠状动脉灌注压（ＣＰＰ）下降及舒张持续时间表示。（２）联合应用ＮＯ合酶及ＰＧＩ２合成酶抑制剂Ｎ－亚硝基－Ｌ－精氨酸（ＬＮＮＡ，０．３ｕｍｏｌ／Ｌ）和ｄｉｃｌｏｆｅｎａｃ（１０ｕｍｏｌ／Ｌ），Ｂｋ引起的冠状动脉舒张反应时相明显缩短（Ｐ＜０．０５～０．００１），而ＣＰＰ降低无明显改变（Ｐ＞０．０５）。（３）上述基础上加用钾通道阻滞剂－阿帕明（１ｕｍｏｌ／Ｌ），结果Ｂｋ引起的ＣＰＰ下降及冠状动脉舒张反应时间均被显著抑制（Ｐ＜０．０５或Ｐ＜０．０１），且该抑制用灌流方法清除阿帕明后解除。（４）应用ＬＮＮＡ－ｄｉｃｌｏｆｅｎａｃ基础上，阿帕明对ＥＤＲＦ类似物—Ｓ－亚硝基－Ｌ－半胱氨酸（１ｎｍｏｌ／Ｌ）引起的ＣＰＰ下降及扩张反应时相均无明显影响（Ｐ＞０．０５）。（５）依次应用ＬＮＮＡ、ｄｉｃｌｏｆｅｎａｃ和阿帕明，基础ＣＰＰ分别提高２９％、８％和６０％。本研究结果提示：①Ｂｋ引起兔冠状动脉阻力血管扩张；②Ｂｋ触发的非Ｅ?

The purpose of the study was to compare the dilatory characteristics of endotheliumderived hyperpolarizing factor (EDHF) with endothe liumderived relaxing factor (EDRF) and prostacyclin (PGI2) in isolated, constantflow perfused rabbit heart. Bradykinin (BK, 33000 pmol/L) was orderly injected in bolus, and repeated under concomitant application of diclofenac and LNNA, then was also applied in administration of diclofenac, LNNA and apamin (1umol/L), an antagonist of K+channel. Furthermore, CYSNO (1nmol/L), an EDRFmimetic, was applied to LNNAdiclofenac resistant relaxation to observe if apamin affects its effect. It showed that apamin had no influence on CYSNO. Finally, LNNA, diclofenac and apamin were orderly used. Results showed a series of dosedependent dilatory responses to Bk in terms of decrease in coronary perfusion pressure (CPP) and time course of relaxation. The time course of the response to Bk was markedly shortened (P<0.05～001) whereas the peak decrease in CPP had no significant change under coadministration of LNNAdiclofenac. In contrast, the decrease in CPP as well as the time course of LNNAdiclofenac insensitive dilatation was significantly blocked by apamin(P<0.05 or P<0.01). Furthermore, apamin played no significant role on dilatation to CYSNO. LNNA,diclofenac and apamin raised basal CPP by 29%, 8% and 60% respectively over control. It is concluded that: (1) There is a LNNAdiclofenac resistant relaxation to Bk in the isolated perfused rabbit heart;(2) EDHF independently contributes to the LNNAdiclofenac insensitive dilatation to Bk probably via hyperpolarization mediated by K+channel; (3) EDHF is specially responsible for the initial phase of the dilatation to Bk whereas contribution to the sustained phase features actions of EDRF and PGI2 ;(4) They jointly maintain the basal tone of the coronary resistance vesels.