摘要
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 endotheliumderived hyperpolarizing factor (EDHF) with endothe liumderived relaxing factor (EDRF) and prostacyclin (PGI2) in isolated, constantflow perfused rabbit heart. Bradykinin (BK, 33000 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, CYSNO (1nmol/L), an EDRFmimetic, was applied to LNNAdiclofenac resistant relaxation to observe if apamin affects its effect. It showed that apamin had no influence on CYSNO. Finally, LNNA, diclofenac and apamin were orderly used. Results showed a series of dosedependent 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<0.05~001) whereas the peak decrease in CPP had no significant change under coadministration of LNNAdiclofenac. In contrast, the decrease in CPP as well as the time course of LNNAdiclofenac insensitive dilatation was significantly blocked by apamin(P<0.05 or P<0.01). Furthermore, apamin played no significant role on dilatation to CYSNO. LNNA,diclofenac and apamin raised basal CPP by 29%, 8% and 60% respectively over control. It is concluded that: (1) There is a LNNAdiclofenac resistant relaxation to Bk in the isolated perfused rabbit heart;(2) EDHF independently contributes to the LNNAdiclofenac 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 PGI2 ;(4) They jointly maintain the basal tone of the coronary resistance vesels.
出处
《中华心血管病杂志》
CSCD
北大核心
1997年第6期453-456,共4页
Chinese Journal of Cardiology
关键词
内皮源性
超极化因子
EDHF
前列环素
缓激肽
Endotheliumderived hyperpolarizing factor
endotheliumderived relaxing factor
prostacyclin bradykinin