Effect of dietary protein content on the structure of blood vessels

It has been demonstrated in experiments on rats that prolonged (for 1-6 months) use of the diet with protein deficiency or excess (5 and 30% respectively as regards caloricity) determines the development of injuries to the aortal wall and arteries of the heart and kidneys. Vascular elasticity shows abnormality, which is the most pronounced if the animals are given the low-protein diet including butter. Sunflower oil has a protective effect which becomes manifest provided that the animals receive the high-protein diet.     

Role of the angiotensin II system in regulation of ovulation and blood flow in the rat ovary

The aim of the present study was to examine the roles of the angiotensin II receptor subtypes, AT(1) and AT(2), in ovulation, and to evaluate the contribution of angiotensin II-mediated pathways in regulation of ovarian blood flow. The AT(1)-specific antagonist, losartan, was administered alone or in combination with the AT(2)-specific antagonist, PD123319, to preovulatory rat ovaries perfused in vitro. Losartan (100 micromol l(-1)) did not affect the number of ovulations, whereas the combination of losartan (100 micromol l(-1)) and PD123319 (10 micromol l(-1)) inhibited ovulation. The angiotensin II antagonists did not affect the ovarian production of oestradiol, progesterone, prostaglandin E(2) (PGE(2)), PGF(2 alpha) or plasminogen activator activity. Ovarian nitric oxide production was inhibited by losartan. Ovarian blood flow was measured by laser Doppler flowmetry in vivo in preovulatory rat ovaries. Intrabursal injection of angiotensin II reduced ovarian blood flow of gonadotrophin-stimulated rats. Losartan had no effect on basal ovarian blood flow but completely blocked the angiotensin II-induced reduction. In contrast, treatment with PD123319 increased basal ovarian blood flow and failed to reverse the effect of exogenously administered angiotensin II, indicating that under physiological conditions, ovarian blood flow of the rat is negatively regulated by angiotensin II mainly through the action of AT(2). Taken together, these results indicate that two different types of angiotensin II receptor facilitate ovulation by cooperative mechanisms and that they regulate ovarian blood flow in a different manner.     

Remodeling and angiotensin II responses of the uterine arcuate arteries of pregnant rats are altered by low- and high-sodium intake

Lowering and increasing sodium intake in pregnant rats evoke opposite changes in renin-angiotensin-aldosterone system (RAAS) activity and are associated with alterations of blood volume expansion. As augmented uterine blood flow during gestation is linked to increased circulatory volume, we wanted to determine if low- and high-sodium intakes affect the mechanical properties and angiotensin II (AngII) responses of the uterine vasculature. Non-pregnant and pregnant rats received a normal sodium (0.22% Na+) diet. On the 15th day of gestation some animals were moved to a low-sodium (0.03%) diet, whereas others were given NaCl supplementation as beverage (saline, 0.9% or 1.8%) for 7 days. All rats were killed after 7 days of treatment (eve of parturition). Uterine arcuate arteries (>100 microm) were set up in wire myographs under a tension equivalent to 50 mmHg transmural pressure. The pregnancy-associated increase in diameter of the uterine arteries was significantly attenuated on the low-sodium diet and 1.8% NaCl supplementation. The arcuate arteries of non-pregnant rats on the low-sodium diet showed markedly increased responses to AngII and phenylephrine (Phe). Pregnancy also resulted in heightened responses to AngII and Phe that were significantly reduced for the former agent in rats on the low-sodium diet. Sodium supplementation of non-pregnant rats did not affect the reactivity of the uterine arteries to AngII, but significantly reduced the effect of Phe (1 micromol/l). High salt also significantly diminished the elevated responses to AngII in the arteries of pregnant animals. It was observed that altered sodium intake affects the mechanical and reactive properties of the uterine arcuate arteries more importantly in pregnant than in non-pregnant rats. Low-salt intake similarly affected the reactivity of the uterine arcuate arteries to AngII and Phe, whereas high-salt intake more specifically affected AngII responses. These results showed that perturbations of sodium intake have major impacts on the structure and functions of the uterine arterial circulation, indicating RAAS involvement in uterine vascular remodeling and function during gestation.     

大豆低聚肽对自发性高血压大鼠血压及血浆血管紧张素的影响

目的：探究大豆低聚肽对于大鼠血压及血浆血管紧张素的影响。方法：采用酶法制备大豆低聚肽,随后进行体外血管紧张素I转换酶（angiotensin I converting enzyme,ACE）活性抑制实验及体内实验,实验设正常对照组（正常血压大鼠（WKY大鼠）饲喂高剂量大豆低聚肽）、阴性对照组（自发性高血压大鼠（SHR大鼠））、阳性对照组（SHR大鼠饲喂卡托普利）和低、中、高剂量组（SHR大鼠饲喂0.90、1.80、4.50 g/kg大豆低聚肽）,喂养30 d后,观察大鼠血压、心率、尿蛋白质量、血管紧张素II质量浓度等指标的变化。结果：大豆蛋白最佳酶解条件为：碱性蛋白酶和中性蛋白酶质量分数各0.1%、50 ℃酶解4 h,此条件下10 mg/mL大豆低聚肽ACE活性抑制率达到71.2%。经饲喂不同剂量大豆低聚肽30 d后,WKY大鼠血压变化不显著（P＞0.05）,SHR大鼠血压有下降趋势;饲喂高剂量大豆低聚肽在第4周时可以显著降低SHR大鼠血压和血管紧张素II质量浓度（P＜0.05）,但对于大鼠心率和尿蛋白质量无显著影响（P＞0.05）。结论：体外实验证明,与大豆蛋白相比,大豆低聚肽对于ACE活性的抑制效果更好;体内实验证明大豆低聚肽可以降低SHR大鼠的血压和血管紧张素II质量浓度,且对正常大鼠血压无明显影响,推测大豆低聚肽通过抑制ACE活性的方式发挥降压功效。     

Antihypertensive and antioxidant effects of the Graptopetalum paraguayense E. Walther extract in spontaneously hypertensive rats

BACKGROUND: Our previous in vitro study showed that 50% ethanolic extract of Graptopetalum paraguayense E. Walther (GE50) exhibited an inhibitory effect on angiotensin I converting enzyme (ACE). This study was aimed at evaluating the antihypertensive and antioxidant effects of GE50 extract on spontaneously hypertensive rats (SHR). RESULTS: Daily oral administration of GE50 extract (2.5 g kg⁻¹ body weight) for 4 weeks exhibited a significant decrease in blood pressure as well as ACE activity of tested tissues in SHR rats, while no significant change was found in normotensive Wistar Kyoto rats (WKY). For SHR, GE50 extract increased the total antioxidant status in the plasma and decreased malondialdehyde levels in all tested tissues. Furthermore, GE50 extract increased α‐tocopherol and glutathione levels in brain tissue, glutathione peroxidase and catalase activities in heart, as well as catalase activity in liver tissue. In WKY rats, GE50 extract only increased ascorbic acid level in liver tissue. CONCLUSION: The present study demonstrated that GE50 might serve as an antioxidant and an ACE inhibitor in convalescence from hypertension in rats. Copyright © 2009 Society of Chemical Industry     

Effect of angiotensin II on ion transport across human Fallopian tube epithelial cells in vitro

Angiotensin II type 1 receptors have been identified in Fallopian tube epithelia. Polarized confluent human Fallopian tube epithelial cell cultures were used under short-circuit conditions to study the actions of angiotensin II on electrogenic ion transport. The results demonstrate that angiotensin II increases baseline short-circuit current, implying a net transport of negatively charged ions from a basal to apical direction. This effect was inhibited by the selective angiotensin II type 1 receptor antagonist losartan. The effects of angiotensin II on short-circuit current were rapid in onset, brief in duration, and although less than those achieved with ATP, similar in amplitude to those described for other epithelia with angiotensin II. These findings reflect a significant retention of function for these cells in monolayer culture. Immunohistochemistry using the antibody 6313/G2, which is directed against a specific sequence in the extracellular domain of the angiotensin II type 1 receptor, confirmed that the receptor was retained in cultured cells. The results indicate that angiotensin II plays a role in regulating the composition of Fallopian tube secretions.     

Inhibition of Angiotensin Converting Enzyme,Angiotensin II Receptor Blocking,and Blood Pressure Lowering Bioactivity across Plant Families

Hypertension is a major risk factor for coronary heart disease, kidney disease, and stroke. Interest in medicinal or nutraceutical plant bioactives to reduce hypertension has increased dramatically. The main biological regulation of mammalian blood pressure is via the renin–angiotensin-aldosterone system. The key enzyme is angiotensin converting enzyme (ACE) that converts angiotensin I into the powerful vasoconstrictor, angiotensin II. Angiotensin II binds to its receptors (AT₁) on smooth muscle cells of the arteriole vasculature causing vasoconstriction and elevation of blood pressure. This review focuses on the in vitro and in vivo reports of plant-derived extracts that inhibit ACE activity, block angiotensin II receptor binding and demonstrate hypotensive activity in animal or human studies. We describe 74 families of plants that exhibited significant ACE inhibitory activity and 16 plant families with potential AT₁ receptor blocking activity, according to in vitro studies. From 43 plant families including some of those with in vitro bioactivity, the extracts from 73 plant species lowered blood pressure in various normotensive or hypertensive in vivo models by the oral route. Of these, 19 species from 15 families lowered human BP when administered orally. Some of the active plant extracts, isolated bioactives and BP-lowering mechanisms are discussed.     

Effect of diets with different content of polyunsaturated fatty acids on ATPase activity in different rat tissues

The authors studied the effect of the diets with varying content of polyunsaturated fatty acids (PUFA) on ATPase activity in the heart, kidneys and lungs of Wistar rats. During 3 weeks the rats received different diets. Group I was kept on the diet poor in PUFA, Group II on the diet rich in linoleic acid, and Group III on the diet rich in linolenic acid. The content of PUFA in food has no effect on ATPase activity in the lungs. The maximal activity of Mg-ATPase in the heart was seen in the Group III rats, while the minimal in the Group I rats (P less than 0.05). On the contrary, Na, K-ATPase activity was minimal in the Group III rats (P-0.05). Examination of ATPase activity in the kidneys has demonstrated no substantial difference between Groups II and III as regards Mg-ATPase activity, whereas Mg-ATPase activity in the Group I animals was significantly reduced (P less than 0.02). As Na, K-ATPase activity in the kidneys increased (Group II, P-0.05) excretion of Na and K with urine considerably diminished.     

Isolation and characterization of angiotensin I-converting enzyme inhibitory peptides from wheat gliadin hydrolysate

Angiotensin I-converting enzyme (ACE) inhibitory peptide was isolated from wheat gliadin hydrolysate prepared with acid protease. Consecutive purification methods were used for peptide isolation including ion-exchange chromatography, size-exclusion chromatography, and reverse-phase high-performance liquid chromatography. The amino acid sequence of this peptide was identified as Ile-Ala-Pro, and the ACE inhibitory activity (IC50 value) was 2.7 microM. The hypotensive activity of Ile-Ala-Pro on spontaneously hypertensive rats was investigated. This peptide inhibited the hypertensive activity of angiotensin I with intravenous injection, and decreased the blood pressure significantly with intraperitoneal administration.     

Optimization and Scale‐Up Preparation of Egg White Hydrolysate with Angiotensin I Converting Enzyme Inhibitory Activity

Angiotensin I converting enzyme (ACE) plays an important role in regulation of blood pressure as it converts angiotensin I into angiotensin II (a potent vasoconstrictor). Food protein‐derived ACE inhibitory peptides have been considered as a safer alternative to antihypertensive drugs. In our previous study, three ACE inhibitory peptides were characterized from egg white ovotransferrin and their antihypertensive activity has been validated in spontaneously hypertensive rats. However, it is too costly to prepare these peptides from purified egg white ovotransferrin. The aims of the study were to determine the feasibility of preparing these peptides using egg white and then to optimize the conditions of preparing egg white hydrolysate. Taguchi's method was used to design experiments for optimization, which was established as follows: substrate %, pH of thermoase, time of thermoase digestion, ratio of pepsin to substrate, pH of pepsin, temperature of pepsin, and time of pepsin digestion were 7.5%, pH 8, 90 min, 1%, pH 2.5, 55 °C, and 180 min, respectively. The ACE inhibitory activity (IC₅₀ value) and peptide yield obtained under optimal condition were 30 ± 2 μg/mL and 77.5% ± 0.3%, respectively, which were comparable to the predicted values. Hydrolysate prepared at 150 L reactor showed comparable activity but low peptide yield. Results of this study demonstrated the feasibility of using egg white protein as the starting material to prepare a functional ingredient with potent ACE inhibitory activity.     

蒙古扁桃药材抗大鼠肾纤维化有效提取物部位的筛选

目的:筛选蒙古扁桃药材抗大鼠肾纤维化的有效提取物部位;方法:采用萃取法制备蒙古扁桃药材石油醚提取物、乙酸乙酯提取物、正丁醇提取物及水部位提取物。70只大鼠随机分组,分别为假手术组、模型组、阳性药组(盐酸贝那普利)、石油醚提取物组、乙酸乙酯提取物组、正丁醇提取物组和水部位提取物组,模型制备采用单侧输尿管结扎术,除了假手术组大鼠只游离单侧输尿管不结扎,其他组别大鼠进行单侧输尿管结扎术。蒙古扁桃药材提取物不同极性部位组均按生药量1.5 g/kg大鼠体重给药。给药21 d后处死大鼠,测定肾纤维化相关指标。结果:石油醚提取物和正丁醇提取物可以增强肾组织及血清中SOD活力,降低组织及血清中MDA水平,降低组织中HYP水平,差异具有显著性(P<0.05);石油醚提取物和正丁醇提取物能够降低血清中肌酐、尿素氮、白蛋白水平。结论:筛选出蒙古扁桃药材石油醚部位和正丁醇部位是抗肾纤维化作用的有效部位。     

葛根煎剂对四氧嘧啶致糖尿病小鼠血糖及其并发症的影响

以四氧嘧啶致小鼠建立糖尿病模型,经葛根煎剂灌胃,连续35 d,每周测定空腹血糖和体重;小鼠在灌胃结束后,断头处死,分别取其胰腺和肾脏做切片进行检查.结果显示:葛根煎剂对糖尿病模型小鼠空腹血糖水平有一定的降低作用,但作用强度较弱;能改善小鼠体质的作用;对肾病并发症有较好的疗效,对被破坏的胰岛细胞有恢复和修复作用.     

百合水提物对对氯苯丙氨酸失眠模型大鼠睡眠改善作用研究

目的 研究不同剂量的百合水提取物对对氯苯丙氨酸(PCPA)失眠模型大鼠睡眠作用的影响。方法 大鼠腹腔注射PCPA混悬液制备大鼠失眠模型。将造模成功大鼠随机分为模型对照组、百合水提物组-低、百合水提物组-中、百合水提物组-高,另设空白对照组。百合水提物组-低 (100 mg/kg.d)、百合水提物组-中(200 mg/kg.d)、百合水提物组-高(300 mg/kg.d)大鼠连续 7 d 给予相应浓度药液,模型对照组和空白对照组连续 7 d 给予生理盐水灌胃。给药期间,观察大鼠一般状态;给药结束后,观察大鼠体质量变化、睡眠潜伏期、总睡眠时间,同时评价不同脑组织中五羟色胺、5-羟基吲哚乙酸、多巴胺含量的变化。结果 百合水提物各剂量组的大鼠在给药期间的一般状态均优于模型组,体质量增加情况也与正常对照组无显著差异;百合水提物中、高剂量组的睡眠潜伏期与模型组相比显著缩短(P＜0.05),百合水提物各剂量组的睡眠时间与模型组相比显著延长(P＜0.05);与模型对照组比较,各给药组大鼠不同脑组织中的5-HT含量显著升高(P < 0.05,P < 0.01),百合水提物中、高剂量组大鼠不同脑组织中的5-HIAA 含量显著升高(P < 0.05,P < 0.01),同时上述２个给药组大鼠的下丘脑、中缝核中的DA含量显著降低(P < 0.05),海马中仅百合水提物高剂量组的DA含量与对照组相比显著降低(P < 0.05)。结论 百合水提物具有改善PCPA失眠模型大鼠睡眠情况的作用。     

Antihypertensive effect and antioxidant activity of peptide fractions extracted from Spanish dry-cured ham

This study examined the antihypertensive and antioxidant activities of water soluble fractions of a Spanish dry-cured ham extract. Antihypertensive activity of a fractionated peptide extract, by size-exclusion chromatography was determined by measuring changes in systolic blood pressure of spontaneously hypertensive rats after oral administration. Every sample exhibited antihypertensive activity, pooled fractions corresponding to 1700 Da or lower were the most antihypertensive with a decrease of 38.38 mm Hg in systolic blood pressure. In vitro experiments revealed marked in vitro angiotensin I-converting enzyme inhibitory activity in fractions corresponding to these elution volumes. Some of the fractions exhibited great 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activity, ranging from 39% to 92% as well as superoxide ion extinguishing ability with values ranging from 41.67% to 50.27% of the antioxidant activity, suggesting the presence of peptides with antioxidant activity. These findings suggest that Spanish dry-cured ham contains peptides with antioxidant and antihypertensive activities.     

血管紧张素转化酶及其活性检测研究进展

血管紧张素转化酶(ACE)是一种哺乳动物组织中普遍存在的,含锌离子的膜结合外肽酶(羧基端二肤),催化血管紧张素Ⅰ水解生成具有血管收缩作用的血管紧张素Ⅱ或水解具有血管收缩功能的缓激肽生成苯丙-精二肽.是高血压、心肌梗死、心力衰竭等治疗药物筛选中的关键酶.本文对ACE的来源分布、化学结构、酶学特性及其检测应用进行综述.     

Angiotensin‐I‐Converting Enzyme Inhibitory Activities and In Vivo Antihypertensive Effects of Sardine Protein Hydrolysate

In our previous study, an antihypertensive protein hydrolysate was prepared from sardine. This study aimed to investigate the composition of sardine protein hydrolysate (SPH) and it's in vivo antihypertensive effect. SPH was separated sequentially with ultrafiltration and size exclusion chromatography. Fractions with high angiotensin‐I‐converting enzyme (ACE) inhibitory activity were further analyzed with RP‐HPLC and amino acids analysis. Then, SPH was individually oral administrated to spontaneously hypertensive rats (SHR) and normotensive wistar kyoto rats (WKY) for 4 wk. After treatment, the systolic blood pressure (SBP), organ index, oxidative status, serum ACE activity, and serum angiotensin‐II (ANG‐II) of all the rats were determined. According to the separation and analysis results, 3 main fractions with high ACE‐inhibitory activity were obtained with different amino acids composition. The animal experiments results showed that SPH could significantly reduce SBP (P < 0.05 or P < 0.01) within 4 h after a single oral administration. After a chronic oral administration, a steady state of SBP in SHR rats was attained. The heart weight index and left ventricular weight index were significantly reduced (P < 0.05) in SPH‐treated SHR rats. The malonyldialdehyde (MDA) levels in organs and serum, serum ACE activity, and serum ANG‐II concentration in SPH‐treated SHR rats were significantly lowered (P < 0.05 or P < 0.01) as compared to their controls. Meanwhile there was no significant effect (P > 0.05) on those parameters in WKY rats. These results indicate that SPH can decrease blood pressure in SHR rats and not in WKY rats.     

血管紧张素转化酶抑制肽稳定性研究

高血压是心血管疾病最重要的且可治疗的危险因素之一,控制高血压是降低心脑血管疾病的发病率、致残率和死亡率的有效措施。血管紧张素转化酶通过影响肾素-血管紧张素系统和激肽释放酶-激肽系统实现对人体血压调节。文章综述了血管紧张素转化酶抑制肽的总体研究趋势、物理化学及酶稳定性的研究现状,并对其值得进一步研究内容进行展望,旨在为血管紧张素转化酶抑制肽的研究与开发提供思路。     

Isolation and characterization of angiotensin I‐converting enzyme inhibitory peptides from wheat gliadin hydrolysate

Angiotensin I‐converting enzyme (ACE) inhibitory peptide was isolated from wheat gliadin hydrolysate prepared with acid protease. Consecutive purification methods were used for peptide isolation including ion‐exchange chromatography, size‐exclusion chromatography, and reverse‐phase high‐performance liquid chromatography. The amino acid sequence of this peptide was identified as Ile‐Ala‐Pro, and the ACE inhibitory activity (IC₅₀ value) was 2.7 μM . The hypotensive activity of Ile‐Ala‐Pro on spontaneously hypertensive rats was investigated. This peptide inhibited the hypertensive activity of angiotensin I with intravenous injection, and decreased the blood pressure significantly with intraperitoneal administration.     

Kinetic changes and antihypertensive effect of aqueous extract of Danggui (Angelica sinensis radix) after stir-fry processing

Danggui (Angelica sinensis Radix) in East Asia for its unique pleasant flavor is usually cooked before utilizing to enhance its tonic effect. To evaluate the quality and bioactivity changes, heat treatments were carried out at 250°C for 0–45 min. 5-Hydroxymaltol, 5-hydroxymethylfurfural, Z-ligustilide, and ferulic acid in aqueous extract of processed danggui (APD) were determined by HPLC while antihypertensive effects were studied after oral administration of APD (50 and 100 mg/kg) for 3 days in spontaneously hypertensive rats (SHR). Compared with aqueous extract of danggui (AD), contents of ferulic acid and Z-ligustilide in APD were significantly decreased but 5-hydroxymaltol and 5-hydroxymethylfurfural were increased. APD could lower blood pressures, plasma renin activities, and angiotensin II levels of SHR, but AD failed to do those. APD exhibited hypotensive effects by regulating renin-angiotensin system and may warrant further evaluation as a potential antihypertensive agent.