高血压是以动脉收缩压或舒张压增高为特征的慢性病,同时是引起多种并发症的心血管疾病[1]。目前,常见的沙坦类、普利类等降血压药都有良好的降压效果,但易引起血胆固醇、甘油三酯升高,提高糖脂代谢异常等糖尿病的发病机率,引发蛋白尿等肾衰竭症状,更严重者还会导致心率过缓、诱发急性心力衰竭[2]。而天然提取的降血压抑制肽生物活性多[3-4]、经济价值高、易消化吸收、安全性高等[5]特点受到广泛关注。围绕食源性血管紧张素转化酶(Angiotensin-I converting enzyme,ACE)抑制肽开发高效的降血压活性产品具有很高的研究价值。但绝大多数抑制肽只在活性上做研究,未能对制备工艺、分离纯化体系作出总结[6]。因此,本文归纳ACE抑制肽的发展及维持血压平衡作用的关系,从ACE抑制肽的工艺制备、分离纯化鉴定、构效关系、体内外活性评价研究方面展开论述,以期为深入研究ACE抑制肽奠定基础。
1 ACE抑制肽概况
ACE属二肽外肽酶,是含锌元素的羧基肽酶。作为机体肾素-血管紧张素系统(Renin-angiotensin system,RAS)中的调节剂,广泛分布于肺、睾丸等组织脏器中[7-8]。在平衡血压方面,血浆中的ACE酶将无活性的十肽血管紧张素Ⅰ(Ang Ⅰ,Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu)的羧基端水解成有活性的八肽血管紧张素Ⅱ(Ang Ⅱ,Asp-Arg-Val-Tyr-Ile-His-Pro-Phe)和二肽的组氨酰亮氨酸(His-Leu),从而促进血管收缩、血压升高。除了诱导血管紧张素Ⅱ收缩外,它还作用于激肽释放酶-激肽系统(Kallikrein-kinin system,KKS) 抑制缓激肽(Bradykinin,BK)分解成无活性片段,也会使血压增高[9] 。
血管紧张素转化酶抑制肽(Angiotensin I-converting enzyme inhibitory peptides,ACEⅠ)是通过抑制Ang Ⅱ的合成或减少缓激肽的释放,从而为降低血压提供有效途径[10]。ACE抑制肽在平衡血压中起到决定性作用。Oshima G等[11]最早是在明胶食物中进行细菌胶原酶降解时获得的ACE抑制肽,通过分析其氨基酸组成和SephadexG-25证实了其6条ACE抑制活性较强序列主要集中在分子量较小的部分;Wang J P等[8]研究的牡蛎纯化ACE抑制肽VVYPWTQRF(Val-Val- Tyr-Pro-Trp-Thr-Gln-Arg-Phe)对小鼠有降压活性。因此,研究ACE抑制肽对高血压患者治疗有积极作用和广阔前景[12]。
2 ACE抑制肽的制备
2.1 酸碱提取法
2.2 微生物发酵法
2.3 虚拟水解法
虚拟水解是利用已知蛋白序列,借助计算机的特定酶解技术进行酶切,将水解得到的特定小肽进行数据库筛选比对[24],找到高活性的多肽,此法可直接获得特定的多肽序列,且抑制活性较好,但模拟筛选的方式较传统酶解方法仍有较多不确定的因素。纪慧卓等[25]基于生物信息学的方式,以大黄鱼为蛋白源虚拟酶解出CMK、GWR、 WAK 和 WQK,其IC50分别为 0.19、2.40、0.40、1.10 mmol/L。于志鹏等[26]虚拟酶解鸡蛋蛋白,通过生物活性、分子质量、水溶性、吸收代谢等性质预测出与ACE能稳定结合的FQK、WGK、ADW,其IC50分别为(250±0.25)、(222.74±1.02)、(85.38±0.54)μmol/L。
2.4 酶解法
3 ACE抑制肽的分离纯化
3.1 膜分离技术
膜分离技术(Membrane separation technique,MST)是多肽的混合物根据不同分子量的孔径大小,通过陶瓷膜和超滤膜等,实现选择性分离的技术,可达到分离提纯的目的[33],其在常温下有效成分损失少、操作方便、浓缩成本低。目前,根据孔径的截留量划分为微滤(Microfiltration,MF)、超滤(Ultrafiltration,UF)、纳滤(Nanofiltration,NF)等。本文介绍的超滤技术是利用膜的两侧能量差作为推动力,通过超滤膜表面的微孔结构,截留分子量范围在1~300 kDa的蛋白质、多肽等分子。Cao D等[34]通过超滤得到>10 kDa、3~10 kDa和<3 kDa三个组分,提取<3 kDa的龙须菜胰蛋白酶多肽液具有(78.15±1.56)%的ACE抑制活性。宋华曾等[35]超滤鱼回(Ictalurus punctatus)鱼皮明胶提取液,得到>3 kDa和<3 kDa两组分多肽,体外活性评价表明<3 kDa的抑制活性优于>3 kDa,并进一步在小鼠体内获得了验证。综上研究表明,小分子量多肽的生物活性优于大分子量多肽[36]。
3.2 凝胶层析技术
3.3 离子交换层析
离子交换层析(Ion-exchange chromatography,IEC)利用蛋白质分子所带电荷的不同这一特性,在一定pH浓度下与离子交换剂进行分离洗脱,从而达到分离提纯的目的[37],但遇到特殊的蛋白结构则难分离。Liu P R等[16]通过固定化金属离子交换纯化了两种新颖的ACE抑制肽His-Leu-His-Thr(HLHT)和Gly-Trp-Ala(GWA),IC50值分别为(458.06±3.24) μmol/L和(109.25±1.45) μmol/L。Wu S G等[40]利用IEC离子交换层析从鱼肉蛋白水解产物中纯化出新型ACE抑制肽Arg-Val-Cys-Leu-Pro(RVCLP),对其进行体外ACE抑制活性研究,测得IC50值为175 μmol/L。
3.4 反向高效液相色谱
反向高效液相色谱法(Reversed-phase high performance liquid chromatography,RP-HPLC)以非极性的反相介质为固定相、极性有机溶剂或其水溶液作为流动相进行溶质的洗脱分离,利用极性较强或亲水的样品分子与反相柱中的固定相结合作用较弱而使溶质较快流出,普遍适用于分离极性、非极性或离子型化合物,具有良好的选择性。Ji W等[41]通过多步纯化得到的超滤水解产物(AKH)在IEC和RP-HPLC技术分离下,得到六肽Lys-Val-Glu-Pro-Leu-Pro,其IC50为(0.93±0.05) mg/mL。
4 ACE抑制肽的鉴定和分子模拟
分离纯化后的多肽,通过对其多肽序列进行鉴定,从而筛选出有ACE抑制作用的氨基酸序列;利用降血压数据库与序列进行比对,将分子模拟技术进一步运用,找到与ACE具有高效相互作用的序列,通过计算机筛选、固相合成出序列,以进行下一步的体外活性实验。
4.1 氨基酸序列的鉴定
4.2 多肽分子模拟
分子模拟是利用计算机以原子水平的分子模型为基础,模拟出分子体系的物理、化学特性,应用于多肽包括分子对接、分子动力学和构效分析等[47]方面的研究。
4.2.1 分子对接
ACE分子对接运用分子模拟软件,主要研究ACE与ACE抑制剂分子间的相互作用,并预测其结合模式和结构功能关系[30,48]。Shi L等[49]对ACE抑制肽NTLTLIDTGIGMTK进行分子对接,得出ACE抑制肽NTLTLIDTGIGMTK可能对ACE的残基Glu123、Glu403、Arg522、Glu376、Gln281和Asn285有抑制作用。Jalkute C B等[50]研究睾丸截短型ACE(tACE)与赖诺普利抑制剂的分子模拟,结果表明tACE的残基Ala 354、Glu 376、Asp 377、Glu 384、His 513、Tyr 520和Tyr 523通过氢键相互作用稳定作用于赖诺普利。王晓丹[51]将YS和INNQFLPYPY通过范德华力和静电力与ACE发生结合,INNQFLPYPY与ACE中部的氨基酸残基His365、Lys522和 His524发生氢键相互作用。
4.2.2 分子动力学
4.2.3 构效分析
定量构效关系(Quantitative structure-activity relationship,QSAR)利用计算机数理统计模型来研究抑制肽的生物活性与分子结构的效应关系以及抑制肽在生物体内吸收、分布、代谢、排泄等生理性质。Shu M等[48]利用偏最小二乘法对58个二肽、55个三肽和50个四肽进行定量结构-活性关系模型表征,QASR的相关系数(r2)分别为0.902、0.985和0.872,交叉验证(q2)分别为0.860、0.951和0.770,结果得出ACE抑制肽序列的疏水性和空间特性在生物活性上起着重要作用。虽然ACE的构效分析并不完善,但ACE抑制肽的活性可能受其氨基酸含量影响,大部分研究也表明含疏水性的羧基端是导致ACE抑制活性的关键[55]。Qi C Y等[56]基于3D-QSAR与分子对接研究含有疏水性残基苯丙氨酸C末端的ACE抑制肽的生物活性,构建了CoMFA(q2 = 0.773,r2 = 0.992)和CoMSIA(q2= 0.664,r2 = 0.990)模型,固相拟合了4种ACE抑制三肽GEF、VEF、VRF和VKF,通过体外活性得出IC50值分别为13、23、5和11 mmol/L,与预测值基本吻合。
5 ACE抑制肽在体内及体外活性评价
检验分离纯化的ACE抑制肽是否具有生物活性,一方面是在体外研究多肽的ACE抑制率及稳定性;另一方面通过构建原发性高血压大鼠(Spontaneously hypertensive rats,SHR) )模型,在体内进行口服灌胃、尾部静脉等实验,以血压值、血清和肺组织中的ACE活性和Ang II含量为指标,探究ACE抑制肽作用机制。
5.1 大鼠体内活性评价
ACE抑制肽体内活性研究多以SHR的血压值为指标,研究其降压活性[57]。Girgih A T等[58]将鲑鱼蛋白SPH进行RP-HPLC分离,得到SF1~SF4组分,将30 mg/kg SF3组分经大鼠口服给药2 h后,结果表明其能降低大鼠血压值(42.1 ± 3.4) mmHg。Lee J K等[29]分离纯化出3个ACE抑制合成肽(Gly-Leu-Pro、Asn-Leu-Pro、Gly-Leu-Pro),其中Gly-Leu-Pro在体内活性和体外功能评价中均表现出降血压的生理功能。张可佳等[59]等将牡蛎ACE抑制肽灌胃大鼠的28 d实验中,第21 天 ACE抑制肽的降压效果显著优于灌胃同等质量的生理盐水,且具有良好的消化稳定性。García-Tejedor A等[60]在牛乳铁蛋白中提取ACE抑制肽,通过口服灌胃10 mg/kg多肽(DPYKLRP、PYKLRP、YKLRP、KLRP、LRP和GILRP)进行SHR血压试验,并在药理水平上研究ACE活性和Ang Ⅱ含量,结果显示DPYKLRP、PYKLRP、YKLRP和LRP均可有效降低血压20~30 mmHg,灌胃DPYKLRP和LRP的ACE活性、Ang Ⅱ含量均降低。
5.2 体外功能活性评价
体外研究检测相对于体内实验操作简单、可靠性强,研究方法主要包括紫外分光光度法、高效液相色谱法等[61]。根据反应体系,ACE抑制剂与ACE酶的活性位点相结合,阻断了Ang II 与失活片段的生成,以马尿酰-组氨酰-亮氨酸(Hip-His-Leu,HHL)为Ang I的模拟物,HHL被ACE分解后生成马尿酸(Hippuric acid,HA)和二肽(His-Leu,HL),通过测定HA的含量分析ACE抑制肽的体外降压活性。Cushuman D W等[61]利用紫外分光光度法,以HHL作为底物添加ACE和ACE抑制肽,通过在λ=228 nm下测定HHL的吸光值来检测ACE抑制肽的活性。Wu J等[33]利用RP-HPLC分离技术,在C18柱上将抑制肽和HHL的反应物通过三氟乙酸、乙腈和水的混合液进行梯度洗脱,定量地分析HHL和HA的峰面积。Wang Y T等[47]通过胃蛋白酶模拟体外消化系统实验,分析5个ACE抑制肽的胃肠道稳定性,其中3个二肽Gln-Trp、Cys-Tyr和Cys-Trp被消化吸收失去活性,另外2个多肽Cys-Met和Cys-Cys则可以抵抗酶的消化作用。赵玉菲等[62]研究体外环境对大海马多肽蛋白PH- I活性的影响,将PH- I分离出PH- I1~ PH- I4结果表明温度对PH-I3活性没有影响,PH-I3多肽在中性和碱性的条件下具有良好的稳定性,但在高糖、高盐下易失活。一些食源性ACE抑制肽具有较高的抑制活性,但经过人体肠胃消化分解后却没有体现出抑制作用,可能的原因之一是氨基酸序列的肽键易受外界肠胃模拟消化系统的蛋白酶水解而导致肽链断裂,从而未形成与ACE有相互作用的肽段[63]。
6 展望
ACE抑制肽日趋成为研究的热点,因其高效的降压作用,可稳定改善大鼠的高血压症状,而受到广泛关注。在体外和体内试验中进一步验证ACE抑制肽具有安全有效、无毒副作用、易消化吸收、长期服用能稳定降压等优点。近年来,随着我国高血压人群数量在不断攀升,开发食源性ACE抑制肽有利于改善服用化学合成抑制剂的高血压患者的多种不良反应。目前,ACE抑制肽在制备工艺、分离纯化技术及构效关系等领域研究较为完善,但仍有不足之处,混合肽制备降压药成本昂贵;分离纯化过程中多肽损失较多;加工环境下多肽活性难以保留,且其在胃肠消化系统中不能稳定被吸收。混合降压肽开发成为天然高效的保健食品还有待进一步探究。因此,鉴定出食源性多肽的氨基酸序列,通过ACE抑制肽与ACE的构效关系分析出高效的纯肽,在药理水平和细胞水平上对纯肽进行降压机理研究,但在保证最大程度地发挥其降压效果等方面还有待进一步研究。
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鸡蛋蛋白ACE抑制肽的筛选、鉴定及其作用机制
[J].借助在线数据库，以鸡蛋蛋白为原料，进行虚拟酶解，通过对活性肽分子质量、生物活性、水溶性及其吸收、分配、代谢、排泄和毒性等性质进行预测，并结合分子对接筛选出与血管紧张素转化酶（angiotensin-? converting enzyme，ACE）稳定结合的3 种ACE抑制肽。FOMC法固相合成三肽FQK、WGK和ADW，并经反相高效液相色谱法测定其体外ACE抑制活性，半抑制浓度分别为（250±0.25）、（222.74±1.02）、（85.38±0.54）μmol/L。分子对接结果表明，FQK、WGK和ADW对ACE的抑制主要归因于能够与ACE的活性口袋S1和S2形成氢键相互作用。本研究为食源性ACE抑制肽的鉴定提供一种高通量筛选方法。
源于海洋贝类蛋白的ACE抑制肽研究现状
[J].ACE抑制肽在血压调节方面起着重要作用，而海洋贝类含有丰富的蛋白质，并具有开发ACE抑制肽的潜能。本文主要简述了源于海洋贝类蛋白源的ACE抑制肽的制备、分离纯化、活性评价及构效关系等方面，以期为海洋贝类蛋白的开发利用提供参考。
海洋多肽功能活性与氨基酸组成的研究进展
[J].海洋生态系统具有高压高盐、常年低温低光照、营养寡且竞争大的特点，因此海洋生物在其生长与代谢过程中产生了大量化学结构特殊、生理活性与功能特殊的物质。其中，海洋生物活性多肽因具有抗高血压、抗氧化、抗凝血以及抗菌等活性，引起了研究者的极大兴趣。目前，从鱼类、贝类、甲壳类等动物中提取的生物多肽或类似物，部分已上市或已进入临床试验阶段。本文主要对这些生物多肽在功能性食品、营养食品和药物中的作用进行综述。
Antihypertensive effect of novel angiotensinⅠconverting enzyme inhibitory peptide from chum salmon(Oncorhynchus keta) skin in spontaneously hypertensive rats
[J].
Structure elucidation of ACE-inhibitory and antithrombotic peptides isolated from mackerel skin gelatine hydrolysates
[J].The fish-processing industry generates significant amounts of waste and by-products that are usually discarded. This study investigated the preparation of bioactive gelatine peptides from fish skin. Gelatine was extracted from mackerel (Scomber scombrus) skin and hydrolysed by pepsin for 1, 2, 6 and 24 h. All hydrolysates were screened for antioxidant, ACE-inhibitory and antithrombotic activities.Gelatine peptides obtained after 24 h of hydrolysis exhibited the highest antioxidant activity (DPPH reduction ∼80%, FRAP ∼130 µmol Trolox equivalent L(-1) ). These hydrolysates had high ACE-inhibitory activity (>70%) and were able to significantly (P < 0.05) inhibit platelet aggregation by about 30%, corresponding to moderate antithrombotic activity.The bioactive properties were mainly due to the presence of low-molecular-weight peptides of 337 and 423 Da.© 2013 Society of Chemical Industry.
Improved method for direct high-performance liquid chromatography assay of angiotensin-converting enzyme-catalyzed reactions
[J].A rapid and sensitive assay was developed for determination of the activity of angiotensin-converting enzyme (ACE) in the presence of inhibitory peptides present in soybean protein hydrolysates. The method utilizes reversed-phase high-performance liquid chromatography (HPLC) to separate and quantify hippuryl-histidyl-leucine (HHL) and hippuric acid (HA). HHL and HA were separated on a Symmetry C18 column by gradient elution that used mixtures of trifluoroacetic acid TFA)-acetonitrile and TFA-water as solvents. Analytical time and baseline separation of HA from HHL were improved over previous HPLC methods. In comparison to the standard spectrophotometric method, the new HPLC method obviates the need for ethyl acetate extraction of HA but requires direct injection of the ACE reaction mixture onto the HPLC column.
Isolation and identification of the angiotensin-Ⅰconverting enzyme(ACE) inhibitory peptides derived from cottonseed protein:optimization of hydrolysis conditions
[J].
Antihypertensive effects of virgin olive oil(unfiltered) low molecular weight peptides with ACE inhibitory activity in spontaneously hypertensive rats
[J].
Purification and identification of angiotensinⅠ-converting enzyme inhibitory peptides and the antihypertensive effect of Chlorella sorokiniana protein hydrolysates
[J].
Purification and charicterization of angiotensinⅠ-converting enzyme(ACE) inhibitory peptides with specific structure X-Pro
[J].This study aimed to specifically prepare angiotensin I-converting enzyme (ACE) inhibitory peptides rich in C-terminal proline from oyster proteins using chymotrypsin and proline-specific endopeptidases (PSEases). The hydrolysates were purified with Sephadex G25, Superdex (TM) 30 Increase 10/300 GL gel filtration chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). The ACE inhibitory IC50 of purified fraction (G1E1C1) was 0.032 +/- 0.003mg/mL. According to ESI-MS and ESI-MS/MS analyses, there were three novel ACE inhibitory peptides in G1E1C1 fraction. Their sequences were Ser-Ala-Pro, Ala-Met-Pro and Thr-Ser-Gly-Pro. Molecular docking of peptides to ACE was studied. Metal-acceptor interactions and conventional hydrogen bonds greatly promoted the stability of peptides to ACE interaction. Pyrrole ring of proline may lead to higher inhibitory activity of peptides. It easily formed a Pi-alkyl interaction with aromatic ring residues (His353, His387, His513, and Phe512). Pi interactions may promote the effect of peptides on ACE. Also, C atom adjacent to the N atom of the pyrrole ring easily formed a carbon hydrogen bond with Ala354. The research discovered three novel ACE inhibitory peptides and provided a method to obtain ACE inhibitory peptides with specific structure X-Pro. The research result played an important role in revealing the structure-activity relationship of ACE inhibitory peptides and designing novel peptides with enhanced biological activity.
Purification and identification of angiotensin-Ⅰconverting enzyme(ACE) inhibitory peptide from lizard fish(Saurida elongata) hydrolysate
[J].
Two novel bioactive peptides from antarctic krill with dual angiotensin converting enzyme and dipeptidyl peptidase Ⅳ inhibitory activities
[J].
AngiotensinⅠ-converting enzyme inhibitory activity and antioxidant capacity of bioactive peptides derived from enzymatic hydrolysis of buffalo milk proteins
[J].
Identification of four new angiotensinⅠ-converting enzyme inhibitory peptides from fermented anchovy sauce
[J].
Predictive modeling of angiotensinⅠ-converting enzyme inhibitory peptides using various machine learning approaches
[J].
Predicting the activity of ACE inhibitory peptides with a novel mode of pseudo amino acid composition
[J].In this study, physicochemical scale (P-scale), was recruited as a novel set of physicochemical descriptors derived from component analysis on four short of physicochemical properties variables (hydrophobic, electronic, steric and hydrogen bond contribution) of 20 coded amino acids, By using partial least squares (PLS), we applied P-scale for the study of quantitative structure activity relationship models (QASRs) on three angiotensin I converting enzyme (ACE) inhibitory peptides datasets (58 dipeptides, 55 tripeptides, and 50 tetrapeptides).The results of QSARs were superior to that of the earlier studies, with correlation coefficient (r(2)) and cross-validated(q(2)) equal to 0.902, 0.86; 0.985, 0.951 and 0.872, 0.77, respectively. By analysis, hydrophobic and steric properties of ACE-inhibitory peptide sequences play important roles in their bioactivities, and novel peptide sequence could be designed based on these properties of the amino acid residues. These results showed that P-scale descriptors can well represent the peptide sequence. Furthermore, the robust models show that P-scale descriptors can be further expanded for polypeptides and can serve as a useful quantitative tool for the rational drug design and discovery.
Characterization of angiotensin-Ⅰconverting enzyme inhibiting peptide from Venerupis philippinarum with nano-liquid chromatography in combination with orbitrap mass spectrum detection and molecular docking
[J].
Molecular dynamics simulation and molecular docking studies of angiotensin converting enzyme with inhibitor lisinopril and amyloid beta peptide
[J].Angiotensin converting enzyme (ACE) cleaves amyloid beta peptide. So far this cleavage mechanism has not been studied in detail at atomic level. Keeping this view in mind, we performed molecular dynamics simulation of crystal structure complex of testis truncated version of ACE (tACE) and its inhibitor lisinopril along with Zn(2+) to understand the dynamic behavior of active site residues of tACE. Root mean square deviation results revealed the stability of tACE throughout simulation. The residues Ala 354, Glu 376, Asp 377, Glu 384, His 513, Tyr 520 and Tyr 523 of tACE stabilized lisinopril by hydrogen bonding interactions. Using this information in subsequent part of study, molecular docking of tACE crystal structure with Aβ-peptide has been made to investigate the interactions of Aβ-peptide with enzyme tACE. The residues Asp 7 and Ser 8 of Aβ-peptide were found in close contact with Glu 384 of tACE along with Zn(2+). This study has demonstrated that the residue Glu 384 of tACE might play key role in the degradation of Aβ-peptide by cleaving peptide bond between Asp 7 and Ser 8 residues. Molecular basis generated by this attempt could provide valuable information towards designing of new therapies to control Aβ concentration in Alzheimer's patient.
Bifunctional peptides with antioxidant and angiotensin-converting enzyme inhibitory activity in vitro from egg white hydrolysates
[J].
Angiotensin converting enzyme(ACE)-peptide interactions:inhibition kinetics,in silico molecular docking and stability study of three novel peptides generated from palm kernel cake proteins
[J].
Studies on the bioactivities of ACE-inhibitory peptides with phenylalanine C-terminus using 3D-QSAR,molecular docking and in vitro evaluation
[J].
Antihypertensive effects of hydrolysates of wakame(Undaria pinnatifida) and their angiotensin-Ⅰ-converting enzyme inhibitory activity
[J].
Kinetics of in vitro enzyme inhibition and blood pressure-lowering effects of salmon( Salmo salar) protein hydrolysates in spontaneously hypertensive rats
[J].
Novel antihypertensive lactoferrin-derived peptides produced by Kluyveromyces marxianus:gastrointestinal stability profile and in vivo angiotensin Ⅰ-converting enzyme(ACE) inhibition
[J].Novel antihypertensive peptides released by Kluyveromyces marxianus from bovine lactoferrin (LF) have been identified. K. marxianus LF permeate was fractionated by semipreparative high performance liquid chromatography and 35 peptides contained in the angiotensin I-converting enzyme (ACE)-inhibitory fractions were identified by using an ion trap mass spectrometer. On the basis of peptide abundance and common structural features, six peptides were chemically synthesized. Four of them (DPYKLRP, PYKLRP, YKLRP, and GILRP) exerted in vitro inhibitory effects on ACE activity and effectively decreased systolic blood pressure after oral administration to spontaneously hypertensive rats (SHRs). Stability against gastrointestinal enzymes suggested that the sequence LRP could contribute to the in vivo effects of parental peptides. Finally, there were reductions in circulating ACE activity and angiotensin II level in SHRs after either DPYKLRP or LRP intake, thus confirming ACE inhibition as the in vivo mechanism for their antihypertensive effect.
Spectrophotoetric assay and properties of the aniotensn converting enzyme of rabbit lung
[J].
