Regulation of endothelial proliferation by the renin-angiotensin system in human umbilical vein endothelial cells

This study was performed in order to evaluate the role of angiotensin II in physiological angiogenesis. Human umbilical vein endothelial cells (HUVEC) were stained for angiotensin II type 1 receptor (AGTR1) immunocytochemically and for gene expression of renin-angiotensin system (RAS) components. The regulation of the angiogenesis-associated genes vascular endothelial growth factor (VEGF) and angiopoietins (ANGPT1 and ANGPT2) were studied using quantitative RT-PCR. Furthermore, we examined the effect of angiotensin II on the proliferation of HUVEC using Ki-67 as well as BrdU immunocytochemistry and investigated whether the administration of the AGTR1 blocker candesartan or the VEGF antagonist FLT1-Fc could suppress the observed angiotensin II-dependent proangiogenic effect. AGTR1 was expressed in HUVEC and the administration of angiotensin II significantly increased the gene expression of VEGF and decreased the gene expression of ANGPT1. Since the expression of ANGPT2 was not affected significantly the ratio of ANGPT1/ANGPT2 was decreased. In addition, a significantly increased endothelial cell proliferation was observed after stimulation with angiotensin II, which was suppressed by the simultaneous administration of candesartan or the VEGF antagonist FLT1-Fc. These results indicate the potential capacity of angiotensin II in influencing angiogenesis by the regulation of angiogenesis-associated genes via AGTR1. Since VEGF blockade opposed the effect of angiotensin II on cell proliferation, it is hypothesised that VEGF mediates the angiotensin II-dependent effect in concert with the changes in angiopoietin expression. This is the first report of the RAS on the regulation of angiogenesis-associated genes in physiology.     

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.     

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 platelet-activating factor on the electrophysiology of the human Fallopian tube: early mediation of embryo-maternal dialogue?

Platelet-activating factor (PAF) is produced by preimplantation embryos and may be involved in the earliest stages of embryo-maternal dialogue. This study explored the potential effects of PAF acting as a signalling agent on human Fallopian tubal epithelial cells grown as a polarized layer in primary culture. The response of the tubal epithelium was assessed in terms of the transepithelial potential difference and short-circuit current (I(scc)), which were recorded using a modified Ussing chamber. Resistance was calculated from the measurements of potential difference and I(scc). PAF (1.9 nmol to 1.9 micromol l(-1)) administered to the apical surface of the cells produced a marked, transient increase in both potential difference and I(scc) in a dose-dependent manner. The mode of action of PAF on the electrophysiological responses of human tubal epithelial cells was investigated. Blockers of Na(+), K(+) and voltage-operated Ca(2+) channels had little effect on PAF action. However, incubation of the epithelial cells in Cl(-)free medium or with a blocker of the Na(+)-K(+)-2Cl(-) cotransporter (Furosemide) reduced the effect of PAF. Blockade of chloride-bicarbonate channels with 4-acetamido-4'-iso-thiocyanostilbene-2.2'-disulphonic acid (SITS) reduced the effect of low doses of PAF only. These results indicate that PAF influences the movement of chloride ions across the tubal epithelial cell and is a candidate molecule for initial embryo-maternal dialogue.     

Production and localization of activins and activin type IIA and IIB receptors by the human endosalpinx

Fallopian tubes from ten premenopausal women were collected and examined for the presence of inhibin, activin and its type IIA and IIB receptors (ActRIIA and ActRIIB) in the endosalpinx. Immunocytochemistry demonstrated clear staining for the betaA, betaB subunits and ActRIIA and ActRIIB that increased in intensity from the isthmus to the ampulla. No staining for the alpha subunit was observed. Whilst the staining of the betaA subunit and ActRIIA was seen in almost every epithelial cell, staining for the betaB subunit and ActRIIB was more variable. In situ hybridization and RT-PCR confirmed the presence of mRNA for the betaA, betaB subunits and ActRIIA and ActRIIB. These results indicated that the epithelium of the uterine tube is able to synthesize activin but not inhibin and has receptors for activin. Activins may thus act as paracrine regulators of tubal epithelial cell function, and embryonic activity may also bind to epithelial receptor and initiate intracellular processes that alter epithelial cell secretions.     

Expression of integrins and extracellular matrix proteins at the maternal-fetal interface during tubal implantation

Investigation of the expression pattern of integrins and their extracellular matrix (ECM) ligands in trophoblasts at the maternal-fetal interface during tubal pregnancy may aid better understanding of the adhesion and invasion of acceptable maternal endometrium by trophoblast cells at the very early stage of human gestation. In this study, spatial and temporal alterations of integrins and ECM ligands were examined in specimens of tubal pregnancies during weeks 3-9 of gestation. In situ hybridization and immunohistochemistry revealed that relatively high levels of integrin alpha(1), beta(1), alpha(5) subunits and heterdimer alpha(5)beta(1) as well as ECM ligands, were displayed in trophoblast cells as early as weeks 3-4 of gestation. Expression peaked during weeks 5-7 and then, with the exception of integrin alpha(1), which remained high, declined slightly up to weeks 8-9 of gestation. Immunoreactive fibronectin, laminin and type IV collagen were detected in column cytotrophoblastic cells (CTB) and some invasive extravillous cytotrophoblast (EVCT) cells and the alterations were coincident with those of the corresponding integrin receptors in EVCT cells. Laminin was strongly stained in EVCT cells that had invaded maternal blood vessels and deep into the interstitium. Maternal epithelial, endothelial and stromal cells also expressed these integrins and ECM ligands. The results indicate their involvement in mediating the adhesion of trophoblasts to the epithelium of the maternal Fallopian tube. The upregulated expression of these molecules in column CTB and invasive EVCT cells may also facilitate the invasion of trophoblasts into the maternal interstitium. Moreover, trophoblasts possessed the potential for self-controlled adhesion and invasion and appear to reach peak invasive capability in the second month of tubal implantation.     

Neurotransmitter-stimulated ion transport across cultured bovine mammary epithelial cell monolayers

Bovine mammary epithelial (BME-UV) and myoepithelial (BMM-UV) cell lines were acquired with the goal of developing an in vitro model of mammary epithelia for the study of ion transport. The bovine mammary cell lines were successfully cultured on commercially available permeable supports, and results suggest that mammary epithelial cells, but not myoepithelial cells, form tight junctions necessary to perform a barrier function. Electrogenic ion transport was not observed in basal conditions. Acute exposure to norepinephrine or forskolin caused prototypic increases in short circuit current accompanied by a reduction in transmural resistance indicative of anion secretion through a conductive pathway. Bumetanide and N-(4-methyphenylsulfonyl)-N'-(4-trifluoro-methylphenyl)urea, inhibitors of Na+/K+/Cl- cotransport and cystic fibrosis transmembrane conductance anion channels, respectively, reduced forskolin-stimulated ion transport. Amiloride, an inhibitor of epithelial sodium channels, had no effect on basal or forskolin-stimulated ion transport. However, naturally occurring and synthetic corticosteroids induced the expression of amiloride sensitive current indicative of sodium absorption. Chronic exposure to increased apical ionic strength and/or reduced carbohydrate concentration were associated with reduced transepithelial resistance although forskolin-stimulated ion transport was unaffected. These results demonstrate that neurotransmitters and steroid hormones act directly on bovine mammary epithelial cells to acutely and chronically modulate the volume and composition of their secretions. The in vitro system that we describe can be further exploited to characterize cellular and molecular mechanisms associated with mammary function in health and disease.     

The role of angiotensin II in the early stages of bovine ovulation

There is evidence that the renin-angiotensin system plays an important role in ovulation in cattle. Using an in vivo model, we investigated the role of angiotensin (Ang) II in bovine ovulation by injecting Ang II receptor antagonists into ovulatory follicles. Animals (n = 102) were pre-synchronized and, when the follicles reached 12 mm, they were given the respective treatment and the cows received GnRH agonist (i.m.) to induce ovulation. The ovulation rate was significantly lower when 100 mu M saralasin (Ang II receptor antagonist) was intrafollicularly injected (14.3%) in comparison with saline solution (83.3%). Based on these results, a second experiment was carried out to determine the timing of Ang II's critical role in ovulation. Saralasin inhibited ovulation only when applied at 0 and 6 h (16.7 and 42.9% ovulation rate in the 0- and 6-h groups respectively), but not at 12 h (100%) following GnRH agonist treatment. To investigate the subtypes of Ang II receptors implicated in the LH-induced ovulation, losartan (LO; AT(1)-Ang II receptor antagonist), PD123 319 (AT(2)-Ang II receptor antagonist), LO+PD123 319, or saline were intrafollicularly injected when the cows were challenged with GnRH agonist. Ovulation was inhibited by PD123 319 and LO+PD123 319 (50.0 and 33.3% on ovulation rate respectively), but not by LO or saline solution (100% ovulation in both groups). From these results, we suggest that Ang II plays a pivotal role in the early mechanism of bovine ovulation via the AT(2) receptor subtype.     

Formation of Fallopian tubal fluid: role of a neglected epithelium

Fluid produced and secreted by the Fallopian tube provides the environment in which gamete transport and maturation, fertilization and early embryo development occur. This review describes the composition of oviductal fluid in terms of ions and nutrients such as glucose, lactate, pyruvate and amino acids. The function of oestrogen-specific glycoprotein is discussed. The mechanisms of fluid secretion and agents known to influence fluid production and secretion are described. Clinical implications of abnormal oviductal fluid production and secretion in hydrosalpinx and pelvic inflammatory disease are also discussed.     

Egg White Ovotransferrin‐Derived ACE Inhibitory Peptide Ameliorates Angiotensin II‐Stimulated Insulin Resistance in Skeletal Muscle Cells

1 Scope

The renin‐angiotensin system (RAS) is a major contributor to the development of insulin resistance and its related complications. Egg white ovotransferrin‐derived tripeptides, IRW (Ile‐Arg‐Trp), IQW (Ile‐Gln‐Trp), or LKP (Leu‐Lys‐Pro) are previously identified as the inhibitors of angiotensin‐converting enzyme (ACE), a key enzyme in the RAS. This study aims at determining whether these peptides are effective in improving insulin resistance, and their mechanisms of action, in a rat derived skeletal muscle cell line (L6 cells).

2 Methods and results

Insulin resistance is induced by treating L6 cells with 1 μm angiotensin II (Ang II) for 24 h. Effects of peptides on glucose uptake are determined using glucose uptake assay, glucose transporter 4 (GLUT4) translocation by immunofluorescence, reactive oxygen species (ROS) by dihydroethidium (DHE) staining, while insulin signaling pathway, Ang II receptor (AT1R or AT2R) levels, and NADPH oxidase activation are measured using Western Blot. Only IRW treatment significantly improves insulin resistance in L6 cells via stimulation of insulin signaling. IRW decreases Ang II‐stimulated AT1R expression, ROS formation, and NADPH oxidase activation.

3 Conclusions

Of three ACE inhibitory peptides studied, only IRW improves insulin resistance in L6 cells, at least partially via reduced AT1R expression and its anti‐oxidative activity.     

Selection of highly fertilization-competent bovine spermatozoa through adhesion to the Fallopian tube epithelium in vitro

Mammalian spermatozoa undergo a marked reduction in number during their journey through the female reproductive tract. One of the checkpoints in the selection of fertilizing spermatozoa may be the transient adhesion to the Fallopian tube epithelium, an event previously shown to play a key role in sperm storage. Bovine spermatozoa adhering to the Fallopian tube epithelium in vitro may be synchronously released by sulphated glycoconjugates. In the present study, experiments were designed to quantify the number of spermatozoa selected through adhesion, and to compare the zona pellucida (ZP) binding and fertilization competence of the initial sperm suspension versus the bound and unbound sperm subpopulations. Results showed that: (1) a fraction accounting for about 30% of the initial sperm suspension was selected by in vitro adhesion to oviductal epithelial cell monolayers; (2) selected spermatozoa, collected after heparin-induced release, had a significantly superior ZP binding and fertilization competence (mean +/- SD: 110 +/- 28 bound spermatozoa per oocyte; % cleavage, mean +/- SEM: 89 +/- 4) compared with both the initial sperm suspension (45 +/- 10 bound spermatozoa per oocyte, P < 0.001; % cleavage: 69 +/- 3, P < 0.05) and the unselected subpopulation (30 +/- 4 bound spermatozoa per oocyte, P < 0.001; % cleavage: 58 +/- 3, P < 0.01). These findings support the hypothesis that binding to oviductal cells is not only beneficial for sperm survival but also represents a crucial step for the selection of spermatozoa endowed with superior fertilization competence.     

奥美沙坦酯药理毒理作用研究进展

奥美沙坦酯是一种选择性的血管紧张素Ⅱ1型受体(AT1)拮抗剂,具有降压作用。本文综述了奥美沙坦酯的药理毒理作用研究进展。     

Postpartum uterine involution in sheep: histoarchitecture and changes in endometrial gene expression

After parturition, the uterus undergoes marked remodelling during involution; however, little is known of the hormonal, cellular and molecular mechanisms that regulate this process. The working hypothesis used in this study is that return of the ovine uterus to a non-pregnant state involves termination of a hormonal servomechanism that regulates endometrial gland morphogenesis and function during pregnancy. Suffolk ewes were ovariohysterectomized on postpartum days 1, 7, 14 or 28. Serum concentrations of oestradiol were high at parturition, declined to postpartum day 4, peaked on postpartum day 6, and then declined and remained low thereafter. Progesterone was undetectable in plasma from ewes post partum. Uterine wet mass and horn length decreased after postpartum day 1, but ovarian mass did not change. Residual placental cotyledons were present in the maternal caruncles on postpartum days 1 and 7 and were extruded by postpartum day 14 as plaques that were resorbed by postpartum day 28. The width of the total endometrium, stratum compactum, stratum spongiosum and myometrium, as well as endometrial gland density, decreased after parturition. Most apoptotic cells in the involuting uterus were large, vacuolated and located between the endometrial glandular epithelial cells on postpartum days 1 and 7. Immunofluorescence analyses identified both T and B cells within the glandular epithelium on postpartum day 1. Cell proliferation was detected in the luminal epithelium and glandular epithelium on postpartum days 1 and 7. On postpartum day 1, expression of oestrogen receptor alpha (ERalpha) was not detected in luminal epithelium and was low in glandular epithelium, but ERalpha was present in epithelia thereafter. Progesterone receptor (PR) protein was not detected in endometrial epithelia on postpartum day 1, but was detected in the glandular epithelium thereafter. Between postpartum days 1 and 7, ERalpha and PR protein increased substantially in the endometrial glandular epithelium. On postpartum days 1-28, abundant expression of oxytocin receptor mRNA was detected in endometrial luminal epithelium and superficial to the middle glandular epithelium. Prolactin receptor (PRLR) mRNA was detected in glandular epithelium on all postpartum days, whereas mRNA for uterine milk protein (UTMP), an index of secretory capacity of glandular epithelium, was present only on postpartum day 1. Collectively, these results indicate that uterine involution in ewes involves remodelling of both caruncular and intercaruncular areas of the uterine wall and termination of differentiated uterine gland functions characteristic of pregnancy.     

Lentil polyphenol extract prevents angiotensin II-induced hypertension, vascular remodelling and perivascular fibrosis

The objective of the study was to investigate whether chronic administration of the Morton lentil polyphenol extract (MLPE), which possesses rich phenolic compounds and a high antioxidant activity, had any protective effects on angiotensin II-induced hypertension. After four weeks of subcutaneous infusion of angiotensin II (200 ng kg(-1) min(-1)) in male SD rats, the water intake and mean artery pressure was significantly increased by 39.8% and 48.3%, respectively, as compared with the control. The media/lumen ratio of the small arteries in the heart and kidneys were increased by 117% and 168% by angiotensin II infusion. The perivascular fibrosis was increased by 65% and 32% in the heart and kidneys, respectively. Levels of the reactive oxygen species in the aorta was enhanced by 115.8%. In another group of rats, which received four weeks of lentil extract administration (1% freeze-dried MLPE in the drinking water), followed by another four weeks of extract administration plus angiotensin II infusion, the angiotensin II-induced enhancement in water intake and mean artery pressures decreased by 12.7% and 8.2%, respectively, as compared with the rats that received angiotensin II infusion alone. The angiotensin II-induced rats showed increases in the media/lumen ratios which were attenuated by 43.6% and 47.2% in the small arteries of heart and kidneys, respectively. Angiotensin II-induced perivascular fibrosis was attenuated by 30% and 26% in the rats that received the extract. Angiotensin II-induced rats showed reactive oxygen species levels in the aorta was reduced by 48.9%. These findings demonstrated that lentil extract attenuated angiotensin II-induced hypertension and associated pathological changes, including remodelling and perivascular fibrosis in the small resistant arteries of heart and kidneys.     

Glycosylation variant analysis of recombinant human tissue plasminogen activator produced in urea-cycle-enzyme-expressing Chinese hamster ovary (CHO) cell line

Tissue plasminogen activator (tPA) was produced in ornithine transcarbamoylase (OTC) cells by introducing the tPA gene into OTC cells. OTC cells were originally derived from Chinese hamster ovary (CHO) cells and express the first two enzymes of the urea cycle, carbamoyl phosphate synthetase I (CPS I) and OTC. To investigate glycosylation variants, tPA variants produced in serum-supplemented culture medium of OTC-tPA cells were separated by lysine-Sepharose 4B chromatography. Unlike in previous studies that used lysine-Sepharose chromatography, two peaks were identified to correspond to eluted glycosylation variants type I and II and type II and the percentages of the type I and type II variants were found to be 23% and 77%, respectively. The biological activities of the type I and II and type II variants were twofold that of the Third International tPA Standard (98/714) produced in the CHO cell line, and the activity of type II variant was 12.6% higher than that of the type I and II variants. These results demonstrate that tPA produced in urea-cycle-enzyme-producing OTC cells have a very high biological activity and the percentage of type II variant which is very valuable for the biopharmaceutical industry is higher than that of any report using CHO cells.     

Polyphenols of Hibiscus sabdariffa improved diabetic nephropathy via regulating the pathogenic markers and kidney functions of type 2 diabetic rats

We recently demonstrated the chemical composition of Hibiscus sabdariffa polyphenol extracts (HPE), and its anti-insulin resistance property using a type 2 diabetic rat model. In the present study, we examined whether HPE prevents diabetic nephropathy, and its putative regulations of the pathogenic markers. HPE significantly inhibited albuminuria and the elevation of clearance of creatinine (CCr) caused by early diabetic nephropathy. Histological findings revealed that HPE inhibited fat deposition and advanced glycation end-products (AGE) expression in kidneys of type 2 diabetic rats. The increase of tubular connective tissue growth factors (CTGFs) and glomerular cluster of differentiation 31 (CD31) were also ameliorated by HPE. HPE reversed collagen accumulation, decreased angiotensin II type 1 receptor (AT-1) elevation, and improved oxidative stress. In conclusion, using the type 2 diabetic model, we have successfully shown that HPE not only has a benefit in reducing hyperglycaemia and hyperinsulinaemia, but can also prevent diabetic nephropathy. HPE has the potential to act as an adjuvant for diabetic therapy, and deserves further investigation.     

Nodal signalling and apoptosis

Nodal, a member of the transforming growth factor beta family, was first cloned from a 7.5 day post-coitum mouse embryo cDNA library. Nodal exerts its biological effects by signalling through its types I and II serine/threonine kinase receptor complex and intracellular Smad proteins. The type II receptors for Nodal are Activin type II receptors ActRIIA and ActRIIB, whereas the putative type I receptors are Activin receptor like kinase (ALK) 4 and ALK7. The main Smad proteins involved in Nodal signalling are Smad2 and Smad3. Studies of Nodal in adult tissues indicate that it is pro-apoptotic in rat ovarian granulosa cells, human trophoblast cells and human ovarian epithelial cancer cells and is growth inhibitory in the latter two cell types. This review summarises the progress made on the functions of Nodal in the apoptosis of adult tissues, especially in the ovary and placenta.     

In vitro development of pig preantral follicles cultured in a serum-free medium and the effect of angiotensin II

A novel culture system is reported in which pig preantral follicles (< 300 microm in diameter) with an intact thecal cell layer were isolated and cultured in a serum-free medium for up to 30 days. The medium supported follicle culture after isolation, while maintaining both somatic cell and oocyte viability. Follicles were cultured in groups (n = 3 per group) on collagen-coated wells for 16 days, during which they retained a three-dimensional structure, maintained oocyte viability and increased in diameter and number of somatic cells. Follicle culture for 30 days resulted in a further increase in number of cells, oocyte viability was maintained, and a significant increase in follicle diameter was observed (P < 0.001), with 29% of follicles forming an antrum. Follicles synthesized measurable quantities of progesterone (168 pg per 100 microl per 48 h; no significant increase with time) and increasing quantities of oestradiol (136 pg per 100 microl per 48 h; P < 0.001 with time). Further supplementation of the medium with 100 micromol testosterone l(-1) at day 28 resulted in a significant increase in oestradiol secretion by both antral (P < 0.01) and preantral follicles (P < 0.05). Culture over 30 days in medium with 10(-10) mol angiotensin II l(-1) and further supplementation at day 28 with 100 micromol testosterone l-1 also increased oestradiol synthesis (P < 0.001). These results show that viable preantral follicles may be cultured for extended periods, and indicate that the possible role of angiotensin II in folliculogenesis and steroidogenesis in early development of pig follicles requires further investigation.     

酿造鲜味酱油调节大鼠血压机制的研究

将雄性SD大鼠随机分成普通饮食（ND）组、高脂和高盐饮食（HFHS）组、高脂和酱油饮食（HFSS）组,连续灌胃10周,测定基础代谢参数及影响血管紧张素及醛固酮分泌的相关生物参数,考察鲜味酿造酱油（盐含量8%）通过肾素-血管紧张素-醛固酮系统（RAAS）调节大鼠血压的机制。结果表明,各组SD大鼠食物摄入量无显著差异（P＞0.05）。与HFHS组相比,HFSS组SD大鼠水摄入量无显著差异（P＞0.05）,体质量、血压显著下降（P＜0.05）,但尿液排出量显著增加（P＜0.05）;血清中总胆固醇、甘油三酯、血管紧张素Ⅱ和醛固酮含量显著下降（P＜0.05）,尿液中的钾离子显著增加（P＜0.05）;肾脏中血管紧张素1型受体、类固醇11β-羟化酶及醛固酮合成酶基因的表达水平显著下降（P＜0.05）,钠钾腺嘌呤核苷三磷酸（ATP）酶α1基因的表达水平显著增加（P＜0.05）,说明酿造鲜味酱油可通过RAAS调节血压。     

Processed dietary plants demonstrate broad capacity for angiotensin converting enzyme and angiotensin II receptor binding inhibition in vitro

While the consumption of fruit and vegetables is protective against cardiovascular disease, the relative efficacy of specific plants is poorly substantiated. In addition, although most plants are consumed in a ‘processed’ state (i.e., including cooking), the bioactivity of processed forms of plants is also generally unknown. Effects on elements of the renin-angiotensin system (RAS) were studied in a selection of 131 dietary plant species, fungi or varietals, across 44 families, after standardised processing. Products were tested for in vitro inhibition of angiotensin converting enzyme (ACE) and of angiotensin II (AngII) binding to its receptor (AT₁R). The results indicated that ACE inhibition activity was weakly correlated with AngII to AT₁R inhibition and that ACE inhibitory activity was positively correlated with total polyphenolic content. These results highlight that processed forms of dietary plants exhibit broad capacity for in vitro modulation of RAS. Furthermore, considering the extensive ACE inhibitory activity reported for peptides derived from many dietary proteins, this implicates broad potential for RAS regulation by several dietary factors. With RAS elements also known to function in the gastro-intestinal (GI) tract, there is a need to understand the physiological role of dietary factors on GI function, blood pressure regulation and salt excretion.