Plasma Angiotensin I-converting Enzyme Research Articles

The role of angiotensin I - converting enzyme (ACE) insertion/deletion gene polymorphism in hypertension and ACE inhibitor therapy: a narrative review

Primary hypertension is the most prevalent type of hypertension, which is primarily attributed to genetic factors. The angiotensin-converting enzyme (ACE) gene has emerged as a prominent candidate among the genetic factors influencing blood pressure regulation. The ACE gene encodes the ACE, which plays a crucial role in the renin-angiotensin system. The ACE gene insertion/deletion (I/D) polymorphism is a variation of the ACE gene that affects blood pressure regulation. Individuals with II, ID, and DD genotypes may exhibit distinct ACE plasma concentrations, potentially contributing to variations in blood pressure levels and response to ACE inhibitor therapy. This article aimed to provide a comprehensive overview of the relationship between the ACE I/D gene with hypertension and angiotensin-converting enzym inhibitor (ACEI) effectiveness. This article presents a narrative review encompassing relevant studies published between 2013 and 2023. A systematic search was conducted using reputable databases such as PubMed, Science Direct, and Scopus. Inclusion criteria were applied, resulting in the selection of 25 articles that met the predefined criteria. The analysis included 25 studies, comprising 5 articles that investigated the impact of ACEI therapy and 20 articles that examined the ACE I/D gene polymorphism in hypertensive populations without ACEI therapy. It can be concluded that compared to the I allele, the D allele of the ACE I/D gene is associated with a higher level of essential hypertension and a reduced ACEI response.

High-volume endurance exercise training stimulates hematopoiesis by increasing ACE NH2-terminal activity.

One of the health benefits of endurance exercise training (ET) is the stimulation of hematopoiesis. However, the mechanisms underlying ET-induced hematopoietic adaptations are understudied. N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits proliferation of early hematopoietic progenitor cells. The angiotensin I-converting enzyme (ACE) NH2-terminal promotes hematopoiesis by inhibiting the anti-hematopoietic effect of Ac-SDKP. Here we demonstrate for the first time the role of ACE NH2-terminal in ET-induced hematopoietic adaptations. Wistar rats were subjected to 10 weeks of moderate-(T1) and high-(T2) volume swimming-training. Although both protocols induced classical ET-associated adaptations, only T2 increased plasma ACE NH2-domain activity (by 40%, P=0.0003) and reduced Ac-SDKP levels (by 50%, P<0.0001). T2 increased the number of hematopoietic stem cells (HSCs; ∼200%, P=0.0008), early erythroid progenitor colonies (∼300%, P<0.0001) and reticulocytes (∼500%, P=0.0007), and reduced erythrocyte lifespan (∼50%, P=0.022). Following, Wistar rats were subjected to T2 or T2 combined with ACE NH2-terminal inhibition (captopril (Cap) treatment: 10 mg.kg-1.day-1). T2 combined with ACE NH2-terminal inhibition prevented Ac-SDKP decrease and attenuated ET-induced hematopoietic adaptations. Altogether, our findings show that ET-induced hematopoiesis was at least partially associated with increased ACE NH2-terminal activity and reduction in the hematopoietic inhibitor Ac-SDKP.

Malaria infection promotes a selective expression of kinin receptors in murine liver

BackgroundMalaria represents a worldwide medical emergency affecting mainly poor areas. Plasmodium parasites during blood stages can release kinins to the extracellular space after internalization of host kininogen inside erythrocytes and these released peptides could represent an important mechanism in liver pathophysiology by activation of calcium signaling pathway in endothelial cells of vertebrate host. Receptors (B1 and B2) activated by kinins peptides are important elements for the control of haemodynamics in liver and its physiology. The aim of this study was to identify changes in the liver host responses (i.e. kinin receptors expression and localization) and the effect of ACE inhibition during malaria infection using a murine model.MethodsBalb/C mice infected by Plasmodium chabaudi were treated with captopril, an angiotensin I-converting enzyme (ACE) inhibitor, used alone or in association with the anti-malarial chloroquine in order to study the effect of ACE inhibition on mice survival and the activation of liver responses involving B1R and B2R signaling pathways. The kinin receptors (B1R and B2R) expression and localization was analysed in liver by western blotting and immunolocalization in different conditions.ResultsIt was verified that captopril treatment caused host death during the peak of malaria infection (parasitaemia about 45%). B1R expression was stimulated in endothelial cells of sinusoids and other blood vessels of mice liver infected by P. chabaudi. At the same time, it was also demonstrated that B1R knockout mice infected presented a significant reduction of survival. However, the infection did not alter the B2R levels and localization in liver blood vessels.ConclusionsThus, it was observed through in vivo studies that the vasodilation induced by plasma ACE inhibition increases mice mortality during P. chabaudi infection. Besides, it was also seen that the anti-malarial chloroquine causes changes in B1R expression in liver, even after days of parasite clearance. The differential expression of B1R and B2R in liver during malaria infection may have an important role in the disease pathophysiology and represents an issue for clinical treatments.

Dietary supplementation with Ethiopian pepper (Xylopia aethiopica) modulates angiotensin-I converting enzyme activity, antioxidant status and extenuates hypercholesterolemia in high cholesterol fed Wistar rats

The lipid lowering, antihypertensive, hepatoprotective and antioxidant activities of Ethiopian pepper (Xylopia aethiopica) supplemented diet in hypercholesterolemic rats were investigated in this study. Animals were divided into five groups (n=7); normal control rats (NC); untreated hypercholeterolemic rats (Hyper-C diet); hypercholesterolemic rats treated with oral dose of 1mg/kg of simvastatin (Hyper-C diet+STATIN); hypercholesterolemic rats treated with 2% (Hyper-C diet+2%ETP) or 4% (Hyper-C diet+4%ETP) supplementation of ETP. ETP-supplemented diets (2% and 4%ETP) reduced total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and concomitantly increased high-density lipoprotein (HDL). There was no significant difference between the TG and LDL levels of groups fed with Hyper-C diet+4%ETP and Hyper-C diet+STATIN. Furthermore, Hyper-C diet+4%ETP significantly reduced plasma angiotensin-I converting enzyme (ACE) levels compared to Hyper-C diet+2%ETP and Hyper-C diet+STATIN. Furthermore, elevated serum levels of ALT, AST and ALP induced by the high cholesterol diet were reversed by ETP and STATIN supplemented diet. Rutin, quercetin and ellagic acid were the dominant phenolic compounds in ETP as revealed by high performance liquid chromatography analysis. The observed hypolipidemic, antihypertensive and hepatoprotective effects exhibited by ETP suggest its potentials to prevent lipid abnormalities and associated risk factors, and this could be attributed to its phenolic constituents.

Mechanism of antihypertensive effect of Mucuna pruriens L. seed extract and its isolated compounds.

Background In the search of safe and effective lead molecules from natural sources, Mucuna pruriens (MP) L. (Fabaceae) seeds were utilized for exploring the antihypertensive potential. Traditionally, it is used as diuretic and hypotensive. Methods Bioassay-guided fractions were utilized for the isolation of active compounds by column chromatography. IC50 value, enzyme kinetics and inhibition mechanism were determined. In vivo time and dose-dependent hypotensive study followed by changes in mean arterial pressure (MAP) induced by angiotensin I (3 nmol/kg), angiotensin II (3 nmol/kg), and bradykinin (10 nmol/kg) in anesthetized rats was done. Plasma and tissue angiotensin I-converting enzyme (ACE) activities were also determined. Results Phytochemical analysis by spectroscopic techniques revealed the presence of known compounds like genistein, ursolic acid and L-DOPA from the ethyl acetate and water fraction, respectively. In vitro study revealed MP ethyl acetate (MPEA) fraction and genistein as the most active fraction (IC50 156.45 µg/mL) and compound (IC50 253.81 µM), respectively. Lineweaver-Burk plots revealed a non-competitive mode of inhibition. ACE protein precipitation was the suggested mechanism for inhibition. The extract showed a time- and dose-dependent decrease in MAP. Genistein was able to dose-dependently reduce the MAP, up to 53±1.5 mmHg (40 mg/kg, i.v.). As compared to control, it showed a dose-dependent decrease in plasma ACE activity of 40.61 % and 54.76 % at 10 mg/kg and 20 mg/kg, respectively. It also decreased the ACE activity in the aorta (107.67nM/ml min at 10 mg, p<0.001; 95.33nM/ml min at 20 mg p<0.001). Captopril was used as a standard for various in vitro and in vivo assays. Conclusions The study revealed the antihypertensive potential of MP seed compounds via ACE inhibition.

ACE insertion/deletion polymorphism and restenosis events after coronary stent placement in East Azerbaijan Province of Iran

Renin-angiotensin system is thought to play a role in coronary thrombosis and restenosis. Plasma angiotensin I-converting enzyme (ACE) activity is associated with an insertion/deletion polymorphism in the gene coding for ACE. The association among restenosis within coronary stents, the D/I polymorphism is analyzed in the present study. We are selected 50 patients who had undergone successful percutaneous transluminal coronary angioplasty, and angiography during 1 year after it for some reason. The I/D alleles were identified on the basis of polymerase chain reaction (PCR) amplification of the respective fragments from intron 16 of ACE gene. The differences between groups were tested by Chi-square test or Fisher exact test. Result from chi-square test and Fisher exact test shows the lack of differences between two groups with respect to sex, age, diabetes, hypertension, cholesterol, hyperlipidemia, stent type, length of stented segment, stent diameter and target vessel. In the second set of analysis, the relationship between genotypes and the outcome variable was tested. These analyses indicated that there were no statistically significant differences the three groups (χ2 (2) = 1.40, p=0 .47). The ACE D/D genotype or D allele does not influence the clinical and angiographic outcome of patients undergoing coronary stent placement. These data suggest that routine determination of the ACE genotype may not help identify patients who are at a higher risk of thrombotic and restenosis events after coronary stent placement.

Angiotensin converting enzyme activity is positively associated with IL-17a levels in patients with schizophrenia

Previous studies of our group showed increased plasmatic Angiotensin-I Converting Enzyme (ACE) activity in schizophrenia (SCZ) patients compared to healthy controls, which was also associated to poor cognitive functioning. The ACE main product angiotensin II (Ang-II) has pro-inflammatory properties. Activated immune-inflammatory responses in SCZ and their association with disease progression and cognitive impairments are also well-described. Therefore, we examined here the association of plasma ACE activity and inflammatory mediators in 33 SCZ patients and 92 healthy controls. Non-parametric correlations were used to investigate the association of the enzyme activity and the peripheral levels of immune inflammatory markers as interleukins, tumor necrosis factor (TNF-α), and interferon (IFN-γ). Although no significant correlations could be observed for ACE activity and measured cytokines levels in healthy controls, a significant positive correlation for ACE enzymatic activity and IL-17a levels was observed in SCZ patients. Correcting for gender did not change these results. Moreover, a significant association for ACE activity and IFN-γ levels was also observed. To our knowledge, this is the first study to show a significant association between higher ACE activity and the levels of cytokines, namely IL-17a and IFN-γ, in patients with SCZ.

Association of insertion–deletion polymorphism of ACE gene and Alzheimer’s disease in Egyptian patients

IntroductionAlzheimer’s disease (AD) is a progressive, neurodegenerative disease. Many studies proposed an association of the insertion (I)/deletion (D) polymorphism (indel) in intron 16 of the gene for angiotensin I-converting enzyme (ACE) on chromosome 17q23 with Alzheimer’s disease. ACE indel and related haplotypes associated with AD risk have reduced plasma ACE whereas protective genotypes have elevated ACE. ObjectTo investigate whether there is a correlation between polymorphisms of the ACE I/D locus gene and AD in Egyptian patients and to determine whether there is a difference in ACE activity in the plasma of clinically diagnosed AD patients. MethodsSubjects of this study are 84 dementia patients diagnosed as having Alzheimer’s disease, 45 males and 39 females aged 65±7years from the Geriatric Department at Ain-Shams University Hospitals and 86 individuals as non dementia controls, 44 males and 42 females aged 63±6years.All subjects were genotyped for the common insertion/deletion polymorphisms for ACE gene locus, and ACE plasma activity assay was measured for AD patients. ResultsThere was statistically significant difference in the frequency of the ACE insertion/deletion alleles between the cases and controls where the I allele distribution in AD cases and controls was 74% vs. 15%, and the I/I genotype frequency was 60% vs. 5%, respectively. They both reached a statistical significance range (I allele frequency: OR=3.714, 95% CI 1.311–10.523, p<0.01; I/I genotype frequency: OR=3.18 95% CI 2.33–4.33, p<0.01). But no significant difference in ACE plasma level was found between different genotypes in our AD patients. ConclusionsOur present study supports the hypothesis of implication (I allele) of ACE gene polymorphism in the development of AD. On the other hand, we did not find significant difference in plasma ACE activities when compared with different studied genotypes.

Preventive and treatment effects of a hemp seed (Cannabis sativa L.) meal protein hydrolysate against high blood pressure in spontaneously hypertensive rats

This work determined the ability of hemp seed meal protein hydrolysate (HMH)-containing diets to attenuate elevated blood pressure (hypertension) development in spontaneously hypertensive rats (SHRs). Effects of diets on plasma levels of renin and angiotensin I-converting enzyme (ACE) in the SHRs were also determined. Defatted hemp seed protein meal was hydrolyzed using simulated gastrointestinal tract digestion with pepsin followed by pancreatin, and the resulting HMH used as a source of antihypertensive peptides. The HMH was substituted for casein at 0.5 and 1.0% levels and fed to young growing rats for 8 weeks (preventive phase) or adult rats for 4 weeks (treatment phase). Feeding of young growing SHRs with HMH resulted in attenuation of the normal increases in systolic blood pressure (SBP) with an average value of ~120 mmHg when compared to the casein-only group of rats (control) with a maximum of 158 mm Hg (p < 0.05). Feeding adult rats (SBP ~145 mmHg) with same diets during a 4-week period led to significant (p < 0.05) reduction in SBP to ~119 mmHg in comparison with 150 mmHg for the control rats. Plasma ACE activity was significantly (p < 0.05) suppressed (0.047-0.059 U/mL) in HMH-fed rats when compared to control rats (0.123 U/mL). Plasma renin level was also decreased for HMH-fed rats (0.040-0.054 μg/mL) when compared to control rats that were fed only with casein (0.151 μg/mL). The results suggest that HMH with strong hypotensive effects in SHRs could be used as a therapeutic agent for both the prevention and treatment of hypertension.

Quantitative Variation in Plasma Angiotensin‐I Converting Enzyme Activity Shows Allelic Heterogeneity in the ABO Blood Group Locus

Angiotensin-I converting enzyme (ACE) occupies a pivotal role in cardiovascular homeostasis. Major loci for plasma ACE have been identified at ACE on Chromosome 17 and at ABO on Chromosome 9. We sought to characterise the genetic architecture of plasma ACE at finer resolution in two populations. We carried out a GWAS in 1810 individuals of Japanese ethnicity; this identified signals at ACE and ABO that together accounted for nearly half of the population variability of the trait. We conducted measured haplotype analysis at the ABO locus in 1425 members of 248 British families using haplotypes of three SNPs, which together tagged the alleles responsible for the principal blood group antigens A1, A2, B and O. Type O alleles were associated with intermediate plasma ACE activity compared to Type A1 alleles (in whom plasma ACE activity was ∼36% lower) and Type B alleles (in whom plasma ACE activity was ∼36% higher). We demonstrated heterogeneity among A alleles: A2 alleles were associated with plasma ACE activity that was very similar to the O alleles. Variation at ACE accounted for 35% of the trait variance, and variation at ABO accounted for 15%. A further 10% could be ascribed to polygenic effects.

A Novel Splice-Site Mutation in Angiotensin I-Converting Enzyme (ACE) Gene, c.3691+1G&gt;A (IVS25+1G&gt;A), Causes a Dramatic Increase in Circulating ACE through Deletion of the Transmembrane Anchor

BackgroundAngiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases.Methods and ResultsTwo Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or cardiovascular disease. The levels of renin-angiotensin-aldosterone system components in the mutated cases and wild-type controls were similar, both at baseline and after 50 mg captopril. Compared with non-affected members, quantification of ACE surface expression and shedding using flow cytometry assay of dendritic cells derived from peripheral blood monocytes of affected members, demonstrated a 50% decrease and 3-fold increase, respectively. Together with a dramatic increase in circulating ACE levels, these findings argue in favor of deletion of transmembrane anchor, leading to direct secretion of ACE out of cells.ConclusionsWe describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences.

Clinical impact of an angiotensin I-converting enzyme insertion/deletion and kinin B2 receptor +9/-9 polymorphisms in the prognosis of renal transplantation

There is a consensus in the scientific literature that supports the importance of the kallikrein kinin and renin angiotensin systems in renal physiology, but few studies have investigated their importance after renal transplantation. The aim of this study was to investigate the clinical effects of the insertion/deletion polymorphism in the angiotensin I-converting enzyme (ACE) gene and the +9/-9 polymorphism in the kinin B2 receptor (B2R) gene in kidney-transplanted patients (n=215 ACE, n=203 B2R) compared with 443 healthy individuals. Demographic results showed that there is a higher frequency of the D allele (high plasma ACE activity) and +9 allele (lower B2R expression) in transplant patients compared with control individuals. We also observed a higher frequency of these alleles in patients who had an elevated level of plasma creatinine. At day 7 post-transplantation, we found a higher prevalence of individuals with the DD genotype with elevated plasma creatinine level. Furthermore, individuals with the DD genotype had a higher chronic allograft dysfunction and graft loss compared with the II patient genotype, which showed no loss of graft. Taken together, our data suggest that the DD genotype is an indicator of an unfavorable prognosis following renal transplantation and could be related to kinin modulation.

No association betweenACEolymorphism and risk of nasopharyngeal carcinoma

Emerging evidence has shown that angiotensin I-converting enzyme (ACE) plays pivotal roles not only in the regulation of cardiovascular homeostasis but also in the process of tumorigenesis. A common ACE I/D polymorphism has been found to be functional, with the D allele displaying a higher plasma ACE level and ACE activity. The purpose of this study was to investigate whether the ACE I/D polymorphism was related to the risk of nasopharyngeal carcinoma (NPC). The study included 175 patients with NPC and 279 age- and sex-matched control subjects. The ACE I/D polymorphism was identified by a polymerase chain reaction analysis. No association was found between the ACE I/D polymorphism and risk of NPC (ID vs. II: odds ratio [OR] = 0.77, 95% confidence interval [CI] 0.51-1.17; DD vs. II: OR = 0.98, 95%CI 0.56-1.72, respectively). This finding indicates that the ACE I/D polymorphism may not play a role in susceptibility to NPC. Further studies are warranted to confirm this finding, especially in ethnically disparate populations.

Strong Association Between Angiotensin I-Converting Enzyme I/D Polymorphism and Unexplained Recurrent Miscarriage of Chinese Women—A Case–Control Study

The patients with recurrent miscarriage (RM) undergo multiple diagnostic tests to detect parental chromosomal anomalies, maternal thrombophilic, endocrine, or immunological disorders, and over 50% of the cases with RM are classified as idiopathic unexplained RM (URM). Angiotensin I-converting enzyme (ACE) is proposed to be a candidate gene in many common diseases, and the plasma ACE levels was associated with an insertion (I)/deletion (D) polymorphism involving about 287 bp situated in intron 16 of the ACE gene, the so-called ACE/ID polymorphism. In this study, we have estimated the ACE I/D polymorphism within a cohort of Chinese patients with URM. There were significant differences both in allele and genotype distribution between patients with URM and healthy controls. The association to URM reached significant both in dominate (1.63-fold, D allele) and in recessive mode (1.76-fold, DD genotype). To our knowledge, the present study is the first to establish the association between ACE I/D polymorphism and the development of URM and indicates that the D allele of the polymorphism possibly be a risk factor for URM in Chinese population.

Characterization of Salt III as new possible allosteric modulator of Angiotensin I Converting Enzyme

Angiotensin I Converting Enzyme (ACE) is a glycoprotein that plays an important function in vascular and electrolyte homeostasis. Recently signaling pathways triggered by ACE was described in endothelial cells, showing that it could be a signaling transducer molecule. Several data demonstrated that inhibitors and substrates of ACE and its product Angiotensin II (AII), evoke intracellular signaling pathways activation. During the study of new AT1 receptor antagonists on blood pressure (BP), our group detected that Salt III had no classical effect in reducing BP in spontaneous hypertensive rats, but increased their BP (6 mmHg) at 15 minutes, suggesting a modulation of ACE activity. Incubating Salt III plus Angiotensin I [AI], and plasma ACE, happened a faster conversion of AI into AII when compared to control (AI plus plasma ACE), in the first 10 minutes of reaction. Pesquero group described that ACE could act as an AII receptor-like. Salt III was able to increase the binding sites of AII with ACE transfected in CHO cells. At the moment we are analyzing JNK and ERK1/2 signaling pathways triggered by ACE activation as result of interaction with Salt III. Salt III that act as an activator of AII binding ACE, and is able to modulate signaling pathways iniciated by ACE could clearly emerge as possible tool for treatment of many disorders such as in diabetes and various renal diseases.

Effects of two training protocols on Angiotensin I-converting enzyme (ACE) activity in horses

Studies in man have shown a correlation between Angiotensin I-converting enzyme (ACE) genetic polymorphisms, ACE activity in the blood and superior athletic performance in sports requiring endurance. It has been hypothesised that the same correlation occurs in horses. There is no information in the literature concerning the effects of training on ACE activity in equine plasma. Exercise training influences the activity of circulating ACE and the response observed is dependent on the exercise protocol. Thirteen horses of mixed breeds were randomly allocated 2 different training protocols to be carried out for a period of 15 weeks. Blood samples were collected from each horse before the beginning of training to determine baseline values. Subsequent sampling took place every 15 days throughout the training phase and for 8 weeks of paddock rest. Angiotensin I-converting enzyme activity was determined by automated spectrophotometry. Training for 15 weeks significantly increased plasma ACE activity, irrespective of training protocol. Differences observed in ACE activity pattern between the 2 training protocols were not statistically significant. Increase in ACE activity peaked with maximum workload. As soon as training was interrupted, ACE levels significantly decreased. Exercise training affects levels of ACE activity in equine plasma. The mechanism for this is not yet elucidated, but cardiovascular adaptation to exercise and blood pressure changes might be involved in this regulation. Exercise training produced a gradual increase in enzymatic activity and might warrant the use of ACE as a tool for fitness monitoring. Angiotensin I-converting enzyme enzymatic activity in the plasma might be directly correlated to a change in genetic expression and that variability must be taken into account when evaluating results from horses undergoing a physical training programme.

ANTIHYPERTENSIVE EFFECT OF MUNG BEAN SPROUT EXTRACTS IN SPONTANEOUSLY HYPERTENSIVE RATS

ABSTRACT We investigated the efficacy of mung bean sprout in reducing hypertension. Different dosages of raw sprout extract (RSE) or dried sprout extracts (DSE) and enzyme-digested sprout extracts were used in a single intragastric administration test to examine the short-term effect in spontaneously hypertensive rats. Results indicated that high doses (600 mg peptide/kg body weight) extracts significantly reduced systolic blood pressure (SBP) of the rats after administration for 6–9, 3–6 and 3–9 h, respectively. Plasma angiotensin I-converting enzyme activities in the treated rats also decreased. A long-term (1 month) intervention study that consists of treatment groups of fresh sprout powder, dried sprout powder and concentrated extracts of the sprouts (RSE and DSE, respectively) was carried out. Results indicated that the sprout powders were not as efficacious as concentrated sprout extracts. SBP of the rats in the RSE and DSE groups were significantly reduced during the intervention period from week 1–4 and week 2–4, respectively. PRACTICAL APPLICATIONS The results suggested that although fresh and low doses of mung bean sprout or sprout extracts did not have apparent antihypertensive effects, high doses of sprout extracts significantly decreased blood pressure in the experimental animals. Therefore, concentrated mung bean sprout juice has potential applications in the preventive management of hypertension. It might be utilized for physiologically functional food with antihypertensive activity.

Leptin regulates ACE activity in mice

Leptin is a hormone related to metabolism. It also influences blood pressure, but the mechanisms triggered in this process are not yet elucidated. Angiotensin-I converting enzyme (ACE) regulates cardiovascular functions and recently has been associated with metabolism control and obesity. Here, we used ob/ob mice, a model lacking leptin, to answer the question whether ACE and leptin could interact to influence blood pressure, thereby linking the renin-angiotensin system and obesity. These mice are obese and diabetic but have normal 24 h mean arterial pressure. Our results show that plasma and lung ACE activities as well as ACE mRNA expression were significantly decreased in ob/ob mice. In agreement with these findings, the hypotensive effect produced by enalapril administration was attenuated in the obese mice. Plasma renin, angiotensinogen, angiotensin I, bradykinin, and angiotensin 1-7 were increased, whereas plasma angiotensin II concentration was unchanged in obese mice. Chronic infusion of leptin increased renin activity and angiotensin II concentration in both groups and increased ACE activity in ob/ob mice. Acute leptin infusion restored ACE activity in leptin-deficient mice. Moreover, the effect of an ACE inhibitor on blood pressure was not changed in ob/+ mice during leptin treatment but increased four times in obese mice. In summary, our findings show that the renin-angiotensin system is altered in ob/ob mice, with markedly reduced ACE activity, which suggests a possible connection between the renin-angiotensin system and leptin. These results point to an important interplay between the angiotensinergic and the leptinergic systems, which may play a role in the pathogenesis of obesity, hypertension, and metabolic syndrome.

Plasma Kallikrein and Angiotensin I-converting enzyme N- and C-terminal domain activities are modulated by the insertion/deletion polymorphism

Angiotensin I-converting enzyme (ACE) is recognized as one of the main effector molecules involved in blood pressure regulation. In the last few years some polymorphisms of ACE such as the insertion/deletion (I/D) polymorphism have been described, but their physiologic relevance is poorly understood. In addition, few studies investigated if the specific activity of ACE domain is related to the I/D polymorphism and if it can affect other systems. The aim of this study was to establish a biochemical and functional characterization of the I/D polymorphism and correlate this with the corresponding ACE activity. For this purpose, 119 male brazilian army recruits were genotyped and their ACE plasma activities evaluated from the C- and N-terminal catalytic domains using fluorescence resonance energy transfer (FRET) peptides, specific for the C-domain (Abz-LFK(Dnp)OH), N-domain (Abz-SDK(Dnp)P-OH) and both C- and N-domains (Abz-FRK(Dnp)P-OH). Plasma kallikrein activity was measured using Z-Phe-Arg-AMC as substrate and inhibited by selective plasma kallikrein inhibitor (PKSI). Some physiological parameters previously described related to the I/D polymorphism such as handgrip strength, blood pressure, heart rate and BMI were also evaluated. The genotype distribution was II n=27, ID n=64 and DD n=28. Total plasma ACE activity of both domains in II individuals was significantly lower in comparison to ID and DD. This pattern was also observed for C- and N-domain activities. Difference between ID and DD subjects was observed only with the N-domain specific substrate. Blood pressure, heart rate, handgrip strength and BMI were similar among the genotypes. This polymorphism also affected the plasma kallikrein activity and DD group presents high activity level. Thus, our data demonstrate that the I/D ACE polymorphism affects differently both ACE domains without effects on handgrip strength. Moreover, this polymorphism influences the kallikrein-kinin system of normotensive individuals.

ACE Insertion/Deletion gene polymorphism and genomic sequence in Diabetic nephropathy

Insertion/deletion polymorphism of the angiotensin I converting enzyme (ACE) genetically determines most of the plasma ACE activity. Modulation of ACE gene activity might have an important bearing on the rate of progression of renal disease, though its exact role in the nephropathy of type 2 diabetes (T2DM) is far from clear. This prospective, cross-sectional, observational study was designed to study the correlation between insertion/deletion polymorphism of ACE gene in diabetic nephropathy. T2DM cases (n=30) were evaluated, regarding duration, onset and degree of albuminuria, renal insufficiency and hypertension. All patients underwent detailed clinical and biochemical evaluation. Genomic DNA intron 16 of the ACE gene was amplified by polymerase chain reaction (PCR) followed by sequencing. The mean age of this study group was 45.21±2.34 yrs. PCR amplification of ACE gene fragments revealed insertion/insertion (I/I, n =8); insertion/deletion (I/D, n = 18) and deletion/deletion (D/D, n = 4) alleles. All three groups were matched age-wise. Micro- and macro-vascular complications were more prevalent in DD type (p=0.012). The majority (75%) of patients with II allele took a longer time to develop overt albumiuria, having lesser hypertension, renal dysfunction, and dyslipidemia than ID and DD allele (p<0.005). On the other hand, urinary albumin excretion, systemic and diastolic blood pressures, triglycerides, serum creatinine and low density lipoprotein-C were significantly higher (p<0.005), in patients of DD type than II and ID groups. This finding suggests that patients with DD allele of the ACE gene are more likely to have progressive diabetic nephropathy with micro- and macro-vascular complications.