Antioxidant, Angiotensin-Converting Enzyme Inhibitory Properties and Blood-Pressure-Lowering Effect of Rice Bran Protein Hydrolysates.

This research aimed to investigate the biological properties of different hydrolysates derived from industrial and laboratory defatted rice bran proteins. Industrial and laboratory defatted rice bran protein concentrates were hydrolyzed with alcalase or flavorzyme. The degree of hydrolysis (DH), oxygen radical absorbance capacity (ORAC), reducing power, total phenolic compounds (TPC), and angiotensin-converting enzyme (ACE) inhibitory activity, were determined in the hydrolysates and the molecular fractions lower than 3 kDa. Systolic blood pressure (SBP) was measured using the tail-cuff method before and after oral administration of 80 mg/kg of different rice bran protein hydrolysate (RBPH) fractions lower than 3 kDa in male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The highest values of in vitro antioxidant activity and TPC were observed in RBPH with alcalase defatted by industry (RBPH2A), and, in all cases, these bioactivities were higher in the molecular fractions lower than 3 kDa. Once again, fractions lower than 3 kDa obtained with alcalase showed a potent ACE inhibitory activity (RBPH1A<3 and RBPH2A<3). The administration of RBPH1A<3 caused a significant decrease in the SBP in SHR, where the maximum decrease was reached at 8 h after administration. SBP in WKY rats was not modified after the administration of RBPH1A<3. These results suggest that the rice bran protein hydrolysates obtained from industry after treatment with alcalase could be an interesting source of bioactive peptides, with potential action on hypertension and other related pathologies.

Evidence that Nitric Oxide is Involved in the Blood Pressure Lowering Effect of the Peptide AVFQHNCQE in Spontaneously Hypertensive Rats.

AVFQHNCQE is an antihypertensive nonapeptide obtained from a chicken foot protein hydrolysate. The present study aims to investigate the mechanisms involved in its blood pressure (BP)-lowering effect. Male (17⁻20 weeks old) spontaneously hypertensive rats (SHR) were used in this study. Rats were divided into two groups and orally administered water or 10 mg/kg body weight (bw) AVFQHNCQE. One hour post-administration, animals of both groups were intra-peritoneally treated with 1 mL of saline or with 1 mL of saline containing 30 mg/kg bw Nω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, or with 1 mL of saline containing 5 mg/kg bw indomethacin, which is an inhibitor of prostacyclin synthesis (n = 6 per group). Systolic BP was recorded before oral administration and six hours after oral administration. In an additional experiment, SHR were administered water or 10 mg/kg bw AVFQHNCQE (n = 6 per group) and sacrificed six hours post-administration to study the mechanisms underlying the peptide anti-hypertensive effect. Moreover, the relaxation caused by AVFQHNCQE in isolated aortic rings from Sprague-Dawley rats was evaluated. The BP-lowering effect of the peptide was not changed after indomethacin administration but was completely abolished by L-NAME, which demonstrates that its anti-hypertensive effect is mediated by changes in endothelium-derived NO availability. In addition, AVFQHNCQE administration downregulated aortic gene expression of the vasoconstrictor factor endothelin-1 and the endothelial major free radical producer NADPH. Moreover, while no changes in plasma ACE activity were observed after its administration, liver GSH levels were higher in the peptide-treated group than in the water group, which demonstrates that AVFQHNCQE presents antioxidant properties.

Dose-Related Antihypertensive Properties and the Corresponding Mechanisms of a Chicken Foot Hydrolysate in Hypertensive Rats.

The antihypertensive properties of different doses of a chicken foot hydrolysate, Hpp11 and the mechanisms involved in this effect were investigated. Spontaneously hypertensive rats (SHR) were administered water, Captopril (50 mg/kg) or Hpp11 at different doses (25, 55 and 85 mg/kg), and the systolic blood pressure (SBP) was recorded. The SBP of normotensive Wistar-Kyoto (WKY) rats administered water or Hpp11 was also recorded. Additionally, plasmatic angiotensin-converting enzyme (ACE) activity was determined in the SHR administered Hpp11. Moreover, the relaxation caused by Hpp11 in isolated aortic rings from Sprague-Dawley rats was evaluated. Hpp11 exhibited antihypertensive activity at doses of 55 and 85 mg/kg, with maximum activity 6 h post-administration. At this time, no differences were found between these doses and Captopril. Initial SBP values of 55 and 85 mg/kg were recovered 24 or 8 h post-administration, respectively, 55 mg/kg being the most effective dose. At this dose, a reduction in the plasmatic ACE activity in the SHR was found. However, Hpp11 did not relax the aortic ring preparations. Therefore, ACE inhibition could be the mechanism underlying Hpp11 antihypertensive effect. Remarkably, Hpp11 did not modify SBP in WKY rats, showing that the decreased SBP effect is specific to the hypertensive state.

Long-term antihypertensive effect of a soluble cocoa fiber product in spontaneously hypertensive rats.

BACKGROUND AND METHODS: This study evaluates the antihypertensive effect of long-term intake of a soluble cocoa fiber product (SCFP). Different doses of SCFP were evaluated (200, 400, and 800 mg/kg/day) and a dose of 800 mg/kg/day of beta-glucan 0.75 (BETA-G) was used as a standard fiber. Water, a neutral vehicle, was used as negative control, and 50 mg/kg/day captopril was used as positive control. Systolic blood pressure (SBP) was measured weekly by the tail cuff method. Body weight, food, and liquid intake were also registered weekly in the rats from 10 to 24 weeks of life. Glucose, total cholesterol, and triglyceride levels; redox status; and the angiotensin-converting enzyme activity were also studied in the plasma samples of these animals. RESULTS: Throughout the 10 weeks of treatment, captopril and SCFP (400 mg/kg/day) demonstrated blood pressure lowering effects in the spontaneously hypertensive rats (p<0.05; n=8). Paradoxically, neither the highest dose (800 mg/kg/day) of SCFP decreased SBP nor 800 mg/kg/day BETA-G (p>0.05; n=8). When the corresponding antihypertensive treatment, was disrupted the SBP values of the 400 mg/kg/day SCFP treated animals returned to control values (p>0.05; n=8). In addition, the SCFP significantly decreased (p<0.05; n=4) the glucose, cholesterol, and triglyceride levels and also the liver and plasma malondaldehyde levels. Moreover, the SCFP slightly increased the reduced glutathione levels in the liver. CONCLUSION: The SCFP could be used to control the blood pressure of hypertensive subjects for a long period of time and could improve metabolic complications associated to cardiovascular diseases.

Probiotic Strain Bifidobacterium animalis subsp. lactis CECT 8145 Reduces Fat Content and Modulates Lipid Metabolism and Antioxidant Response in Caenorhabditis elegans.

Recently, microbial changes in the human gut have been proposed as a possible cause of obesity. Therefore, modulation of microbiota through probiotic supplements is of great interest to support obesity therapeutics. The present study examines the functional effect and metabolic targets of a bacterial strain, Bifidobacterium animalis subsp. lactis CECT 8145, selected from a screening in Caenorhabditis elegans. This strain significantly reduced total lipids (40.5% ± 2.4) and triglycerides (27.6% ± 0.5), exerting antioxidant effects in the nematode (30% ± 2.8 increase in survival vs control); activities were also preserved in a final food matrix (milk). Furthermore, transcriptomic and metabolomic analyses in nematodes fed with strain CECT 8145 revealed modulation of the energy and lipid metabolism, as well as the tryptophan metabolism (satiety), as the main metabolic targets of the probiotic. In conclusion, our study describes for the first time a new B. animalis subsp. lactis strain, CECT 8145, as a promising probiotic for obesity disorders. Furthermore, the data support future studies in obesity murine models.

The blood pressure effect and related plasma levels of flavan-3-ols in spontaneously hypertensive rats.

We studied the short-term antihypertensive effect of flavan-3-ols (-)-epicatechin, (+)-catechin and (-)-catechin, in spontaneously hypertensive rats (SHR). Plasma metabolites and the corresponding plasma antioxidant capacity were determined. All the assayed flavan-3-ols decreased systolic blood pressure (SBP) in SHR. Their antihypertensive effects were less pronounced than that of Captopril (50 mg kg(-1)) and were not shown in normotensive Wistar-Kyoto rats. 6 mg kg(-1) (-)-epicatechin caused the maximum decrease in SBP. The maximum effects of the catechin monomers were observed post-administration of 0.5 mg kg(-1) of flavan-3-ols, (-)-catechin being the least effective among the three assayed compounds. Glucuronide and methyl glucuronide metabolites were obtained in the flavan-3-ol treated SHR, but it was not possible to relate the antihypertensive effect of the assayed flavan-3-ols with a concrete plasma metabolite or with their antioxidant effect. In conclusion, the studied flavan-3-ols could be responsible for the antihypertensive effect of cocoa products.

Long-Term Effect of an Aqueous Fraxinus excelsior L. Seed Extract in Spontaneously Hypertensive Rats.

The effect of long-term intake of different doses (20, 40, and 60 mg/kg/day) of a Fraxinus excelsior L. seed extract (FESE) on spontaneously hypertensive rats (SHR) was evaluated. Water was used as control and captopril (50 mg/kg/day) was used as positive control. Systolic blood pressure, body weight, and food and liquid intake were registered weekly in SHR. The antioxidant and vascular relaxing properties of FESE were also studied in these animals. The development of hypertension was attenuated in the groups treated with captopril or FESE. The antihypertensive effect was more accentuated in the captopril group than in the FESE groups, and it was paradoxically more accentuated in the groups treated with 20 mg/kg/day or 40 mg/kg/day of FESE than in the group treated with the highest dose of this extract. Body weight gain and food intake increased in the FESE groups. After removing the corresponding antihypertensive treatment, the arterial blood pressure and the body weight of the FESE treated animals returned to control values. In addition, FESE increased plasma antioxidant capacity and decreased plasma and liver malondialdehyde levels. Moreover, acetylcholine relaxation improved in the aorta rings from the FESE treated rats.

Beneficial effects of polyphenols on cardiovascular disease.

In recent years, numerous studies have demonstrated the health benefits of polyphenols, and special attention has been paid to their beneficial effects against cardiovascular disease, the leading cause of death in the world today. Polyphenols present vasodilator effects and are able to improve lipid profiles and attenuate the oxidation of low density lipoproteins. In addition, they present clear anti-inflammatory effects and can modulate apoptotic processes in the vascular endothelium. It has been suggested that most of these effects are a consequence of the antioxidant properties of polyphenols, but this idea is not completely accepted, and many other mechanisms have been proposed recently to explain the health effects of these compounds. In fact, different signaling pathways have been linked to polyphenols. This review brings together some recent studies which establish the beneficial properties of polyphenols for cardiovascular disease and analyzes the mechanisms involved in these properties.

Dietary fiber, gut peptides, and adipocytokines.

The consumption of dietary fiber (DF) has increased since it was related to the prevention of a range of illnesses and pathological conditions. DF can modify some gut hormones that regulate satiety and energy intake, thus also affecting lipid metabolism and energy expenditure. Among these gut hormones are ghrelin, glucagon-like peptide 1, peptide YY, and cholecystokinin. Adipose tissue is known to express and secrete a variety of products known as "adipocytokines," which are also affected by DF. Some of the most relevant adipocytokines include adiponectin, leptin, tumor necrosis factor-α, and interleukin-6. The release of adipocytokines, by either adipocytes or macrophage-infiltrated adipose tissue, leads to a chronic subinflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes, therefore increasing the risk of cardiovascular disease associated with obesity. DF modulation of these molecules could also have positive effects on obesity, insulin resistance, and hyperlipidemia. This review is focused on the effects of DF on the above-mentioned gut peptides and adipocytokines.

Soluble fiber-enriched diets improve inflammation and oxidative stress biomarkers in Zucker fatty rats.

In this study we evaluated the effect of the administration of different soluble fiber enriched-diets on inflammatory and redox state of Zucker fatty rats. Four groups of ten 8 week-old female Zucker fatty rats were used. The four groups were respectively fed the following diets until the 15th week of life: standard diet (obese control), 10% high methoxylated apple pectin (HMAP)-, 5% soluble cocoa fiber (SCF)-, and 10% ß-glucan-enriched diets. A group of Zucker lean rats fed the standard diet was also used as control for normal values of this rat strain. The plasma levels of tumoral necrosis factor-α (TNF-α), adiponectin, and malondialdehyde (MDA) were measured at the end of treatment. The reduced glutathione liver levels were also obtained at that moment. TNF-α plasma levels decreased somewhat in Zucker fatty rats fed the different fibers, and MDA plasma levels significantly decreased in these animals. Nevertheless, adiponectin plasma levels increased in the Zucker fatty rats fed the SCF enriched diet, but did not change in the HMAP and the ß-glucan group. The Zucker fatty rats fed the different fiber showed a trend towards increased the reduced glutathione liver levels, but significant differences with obese control rats were only obtained in the ß-glucan group. The results obtained in this study suggest that the intake of the different soluble fiber-enriched diets that we have evaluated could prevent and/or attenuate the inflammatory and/or the prooxidative state of the metabolic syndrome.

Effect of a soluble cocoa fiber-enriched diet in Zucker fatty rats.

The effects of a soluble cocoa fiber (SCF) were studied in Zucker fatty rats. Two groups of Zucker fatty rats were fed the following diets: standard diet and 5% SCF-enriched diet. A group of Zucker lean rats fed the standard diet was used for results comparison with obese Zucker animals. Solid and liquid intakes, body weight, plasma glucose, lipid profile, and systolic (SBP) and diastolic (DBP) blood pressure were recorded weekly. At the end of the experimental period insulin was determined, and fat apparent digestibility (FAD) and insulin resistance were calculated. The Zucker fatty rats fed 5% SCF-enriched diet showed less weight gain and food intake than those fed the standard diet. The group fed the fiber-enriched diet showed lower values of the total cholesterol/high-density lipoprotein cholesterol ratio and triglyceride levels than the standard group. FAD was also lower in the fiber group. Both SBP and DBP were decreased. In addition, SCF reduced plasma glucose and insulin, and as a consequence the insulin resistance was also decreased. Our data demonstrate that SCF resulted in an improvement of the studied risk factors associated with cardiometabolic disorders.

Changes in arterial blood pressure after single oral administration of milk-casein-derived peptides in spontaneously hypertensive rats.

In this study we evaluated the short-term oral antihypertensive effect of several peptide sequences isolated from casein fractions, previously characterized as in vitro angiotensin-converting enzyme-inhibitors, in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) and the diastolic blood pressure (DBP) of the rats were measured by the tail cuff method before administration and also 2, 4, 6, 8 and 24 h post-administration. The sequences LVYPFTGPIPN, HLPLP, IAK, YAKPVA and WQVLPNAVPAK showed a clear decrease in SBP and DBP in SHR. HPHPHLSF caused a significant decrease of the DBP in the SHR, but this sequence did not modify the SBP of these animals in a significant manner. KKYNVPQL did not modify SBP in the SHR, and caused a slight, but significant and maintained, decrease in DBP in these animals. SBP and DBP returned to baseline values 24 h post-administration of all peptides. In conclusion, these peptides are bioactive ingredients with potential benefit in the prevention and treatment of hypertension or other associated disorders.

Antihypertensive effect of a polyphenol-rich cocoa powder industrially processed to preserve the original flavonoids of the cocoa beans.

A natural flavonoid-enriched cocoa powder, commercially named CocoanOX and developed via a patented industrial process, was characterized and tested for a possible antihypertensive effect. The bioavailability of this polyphenol-rich cocoa powder developed at pilot scale was previously demonstrated in humans. The present results showed that this product was very rich in total procyanidins (128.9 mg/g), especially monomers, dimers, and trimers (54.1 mg/g), and mainly (-)-epicatechin (19.36 mg/g). The effect of a single oral administration of CocoanOX in spontaneously hypertensive rats (SHR) was evaluated at different doses (50, 100, 300, and 600 mg/kg). This product produced a clear antihypertensive effect in these animals, but these doses did not modify the arterial blood pressure in the normotensive Wistar-Kyoto rats. Paradoxically, the maximum effect in the systolic blood pressure (SBP) of SHR was caused by 300 mg/kg of CocoanOX. This dose brought about a decrease in this variable very similar to that caused by 50 mg/kg Captopril. It was also surprising that the maximum effect in the diastolic blood pressure (DBP) was caused by 100 mg/kg CocoanOX. The initial values of DBP and SBP were recovered in SHR, respectively, 24 and 48 h postadministration of the different doses of CocoanOX or Captopril. These results suggest that CocoanOX could be used as a functional ingredient with antihypertensive effect, although it would be also necessary to carry out bioavailability and clinical studies to demonstrate its long-term antihypertensive efficiency in humans.

Dietary fiber in the prevention and treatment of metabolic syndrome: a review.

Inclusion of fiber in the diet has been linked to the prevention of a range of illnesses and conditions. This review contains several ideas about the possible benefits of dietary fiber intake in patients with metabolic syndrome. The principal beneficial effects of a fiber-rich diet in these patients are: prevention of obesity, improved glucose levels, and control of the profile of blood lipids. We now also know that dietary fiber may favor the control of arterial blood pressure. Animal experiments have also shown the benefit of different types of fiber on these variables. Of particular relevance are the studies using obese Zucker rats, which present similar anomalies to those seen in patients with metabolic syndrome. There is therefore a growing interest in discovering new sources of natural fiber. Some of these different kinds of fiber may then be used as functional ingredients to obtain foods with properties that are beneficial to health.

Ratas Zucker como modelo experimental para el estudio de diferentes enfermedades / Zucker rats as an experimental model for the study of various diseases

Las ratas Zucker obesas son el modelo animal mejor conocido de obesidad genética. La obesidad en estos animales se hereda como carácter autosómico recesivo. Las ratas afectadas presentan una mutación en el receptor de leptina y acusan hiperfagia y otras alteraciones semejantes a las que aparecen en el síndrome metabólico humano. Estos animales presentan hiperinsulinemia, por lo que se los puede considerar también un modelo de resistencia a la insulina. Su utilidad como modelo de diabetes mellitus tipo 2, sin embargo, es cuestionable, pues presentan sólo ligera intolerancia a la glucosa. El perfil lipídico de estos animales también está alterado. Hay aumento de lipoproteínas de muy baja densidad (VLDL) y de alta densidad (HDL), pero no aumenta el colesterol de las lipoproteínas de baja densidad y no se los puede utilizar como modelo de aterogénesis. Tampoco se los considera un modelo de hipertensión, aunque pueden presentar valores altos de presión arterial sistólica a partir de las 28 semanas de vida (AU)

Zucker fatty rats are the best known animal model of genetic obesity. Obesity in these animals is inherited as an autosomal recessive trait. Affected rats have a mutation in the leptin receptor and show hyperphagia and other alterations similar to those that appear in human metabolic syndrome. These animals have hyperinsulinemia and can also be considered a model of insulin resistance. Nevertheless, the usefulness of Zucker fatty rats as a model of type 2 diabetes is questionable, since these animals have only mild glucose intolerance. The lipid profile in these animals is also altered. These rats show an increase in both very low density lipoproteins (VLDL) and high density lipoproteins (HDL) but no increase in LDL cholesterol and these animals cannot be used as a model for atherogenesis. Zucker obese rats are not a model for hypertension either, even though they show high systolic blood pressure values after 28 weeks of life (AU)

Zucker rats as an experimental model for the study of various diseases.

Zucker fatty rats are the best known animal model of genetic obesity. Obesity in these animals is inherited as an autosomal recessive trait. Affected rats have a mutation in the leptin receptor and show hyperphagia and other alterations similar to those that appear in human metabolic syndrome. These animals have hyperinsulinemia and can also be considered a model of insulin resistance. Nevertheless, the usefulness of Zucker fatty rats as a model of type 2 diabetes is questionable, since these animals have only mild glucose intolerance. The lipid profile in these animals is also altered. These rats show an increase in both very low density lipoproteins (VLDL) and high density lipoproteins (HDL) but no increase in LDL cholesterol and these animals cannot be used as a model for atherogenesis. Zucker obese rats are not a model for hypertension either, even though they show high systolic blood pressure values after 28 weeks of life.

Effect of the long-term intake of an egg white hydrolysate on the oxidative status and blood lipid profile of spontaneously hypertensive rats.

This paper examines the effects of the long-term consumption of egg white hydrolysed with pepsin (hEW) on the antioxidant status and lipid profile of spontaneously hypertensive rats (SHR). The antioxidant capacity was measured by the oxygen radical absorbance capacity (ORAC) and the oxidative status by the malon-dialdehyde (MDA) assay. The lipid profile was analysed spectrophotometrically. The radical-scavenging capacity of the plasma was increased and the MDA concentration in the aorta was decreased in the SHR treated with 0.5g/kg/day of hEW. Our findings indicate that hEW played an important role in antioxidative defence of SHR and exerted a beneficial effect on the lipid profile, lowering triglycerides and total cholesterol without changing HDL levels. Therefore, hEW may be useful to prevent or reverse abnormalities associated with the metabolic syndrome and its complications, such as hypertension, oxidative stress and hyperlipidemia.

Vascular effects, angiotensin I-converting enzyme (ACE)-inhibitory activity, and antihypertensive properties of peptides derived from egg white.

In this study, we have identified novel antihypertensive peptides derived from egg-white proteins. The sequences YRGGLEPINF and ESIINF produced an acute blood-pressure-lowering effect in spontaneously hypertensive rats upon a single oral administration. Our results suggest that the antihypertensive action could be attributed to a vascular-relaxing mechanism that would occur in vivo independently of angiotensin I-converting enzyme (ACE) inhibition, because neither these peptides nor their main digestion fragments, except for the dipeptide YR, acted as ACE inhibitors in vitro. The vasodilator and antihypertensive activity of the sequences ESI and NF would explain the blood-pressure-lowering effect of ESIINF. With regard to YRGGLEPINF, in addition to NF, YR appeared as the main fragment responsible for its activity. The dipeptide YR, named kyotorphin and previously identified as an endogenous analgesic neuropeptide in the central nervous system, showed strong vasodilator and antihypertensive properties. The structure-activity features of the vasodilator peptides are discussed.

Síndrome metabólico / Metabolic syndrome

El síndrome metabólico se considera una asociación de problemas de salud que tienen como componente patogénico fundamental la resistencia a la insulina. El diagnóstico implica 3 o más de los siguientes factores de riesgo: obesidad abdominal, triglicéridos altos, colesterol delas lipoproteínas de alta densidad bajo, hipertensión e hiperglucemia en ayunas. El síndrome se relaciona con cambios en la proliferación del músculo liso vascular y con crecimiento y disfunción endotelial. Los adipocitos de estos pacientes segregan ácidos grasos libres y moléculas biológicamente activas; entre ellas, factor de necrosis tumoral alfa, leptina y adiponectina. El paciente debe enfrentarse con un cambio de hábitos ensu alimentación y actividad física. Para la dislipemia se utilizan estatinas y fibratos; para mejorar la sensibilidad a la insulina, biguanidas y tiazolidinedionas. Como antihipertensivos se recomienda fármacos que inhiban la formación o los receptores de la angiotensina II (AU)

Metabolic syndrome is described as a group of health problems whose fundamental pathogenic component is insulin resistance. Diagnosis involves the presence of 3 or more of the following risk factors: abdominal obesity, high triglyceride levels, low high-density lipoprotein cholesterol, hypertension, and fasting hyperglycemia. This syndrome is associated with changes in vascular smooth muscle proliferation, stimulus of endothelial growth, and endothelial dysfunction. The adipocytes of patients with metabolic syndrome segregate free fatty acids and biologically active molecules, such as tumor necrosis factoralpha, leptin and adiponectin. These patients should alter their eating and exercise habits. Statins and fibrates are administered for dyslipidemia. To improve insulin sensitivity, biguanides and thiazolidinediones are used. The recommended anti-hypertensive agents are angiotensin-converting enzymeinhibitors and angiotensin II type 1 receptor antagonists (AU)

Angiotensin-converting enzyme activity in plasma and tissues of spontaneously hypertensive rats after the short- and long-term intake of hydrolysed egg white.

This paper evaluates the effects of the short- (1 g/kg) and long-term (0.5 and 1 g/kg/day) oral intake of egg white hydrolysed with pepsin (hEW) and the long-term oral intake (1 g/kg/day) of egg white (EW) on local angiotensin-converting enzyme (ACE) activities in plasma and other tissues of spontaneously hypertensive rats (SHR), as compared to the effect of the ACE inhibitor prototype captopril. The rats treated with hEW were classed in a different group than the control rats and the rats treated with EW by cluster analysis, taking into account their tissue ACE activities and their systolic blood pressure (SBP). Principal component analysis (PCA) showed that SBP in SHR was negatively related with ACE activity in plasma and positively related with ACE activity in aorta and kidney. ACE activity in plasma significantly increased after the long-term treatment with hEW (0.5 g/kg/day). ACE activity in aorta and kidney was significantly inhibited 4 h after the short-term administration of hEW. The long-term treatment with hEW caused local effects on ACE activity in aorta, kidney and lungs that followed a pattern similar, but less pronounced, than that caused by captopril.