内皮衍生舒张因子合成前体降压机制的研究

Thehypotensivemechanismofthesubstratesynthesizingendotheliumderivedrelaxingfactor

本研究试图探讨内皮衍生舒张因子（ＥＤＲＦ）合成前体——左旋精氨酸（Ｌ－Ａｒｇ）的降压机制。从实验动物、临床及离体与整体功能上观察其血液动力学效应。结果显示：给予自发性高血压大鼠（ＳＨＲ）和ＥＤＲＦ合成抑制剂——左旋硝基精氨酸（Ｌ－ＮＮＡ）诱导的高血压大鼠，以及高血压病（ＥＨ）患者静脉滴注Ｌ－Ａｒｇ，均能产生明显的降压作用，其大鼠主动脉环对去甲肾上腺素（ＮＥ）及内皮素（ＥＴ）收缩反应明显减低，对乙酰胆碱（Ａｃｈ）的舒张反应明显增强，ＥＨ患者的心排血量明显增加，外周血管阻力明显减低，并伴有体内主要的收缩因子ＥＴ水平明显下降，ＥＤＲＦ效应产物ｃＧＭＰ明显升高，且尿亚硝酸盐试验阳性。结论：本研究提示Ｌ－Ａｒｇ通过增加体内ＥＤＲＦ的合成释放，产生有效的降压作用。

Aim:ThehypotensivemechanismofL-arginine,thesubstrateforsynthesizingen-dotheliumderivedrelaxingfactor(EDRF)wasstudied.Methods:TheefectsofL-arginineinisolat-edaorticringandintactratswerestudiedaswelaspatientswithhypertension.Results:L-argininewasadministratedbyintravenousdriptoSHR(spontaneouslyhypertensiverats),hypertensiveratsinducedbyL-NNAandesentialhypertensivepatientsrespectively,alofwhichshowedthatthebloodpresurewassignificantlylowered.TheconstrictingresponseofaorticringsoftheratstoNE(norepinephine)andET(endothelin)wasdecreased,andtherelaxingresponseofaorticringsoftheratstoAch(acetylcholine)increased;thecardiacoutputincreasedandthetotalperipheralresistancedecreasedinthehypertensivepatients,accompaniedwiththedecreaseofthelevelofETwhilethelevelofcGMPonefectiveproductsofEDRFaugmentedandacompaniedwithpositiveurinenitratesinEHandL-argininegroup.Conclusion:TheaboveresultsprovidedtheevidencethatsystemicL-arginineadministrationcausesanamountofEDRFreleasesuficienttocausevasodilationandhy-potensioninhypertensiveanimalsandpatients.