Influence of Angiotensin-Converting Enzyme Inhibitors (ACEi) on Angiogenesis Induced by Physical Exercise

Angiotensin-converting enzyme inhibitors (ACEi) are used to reduce blood pressure and vascular resistance by modulating the ACE activity responsible for the angiotensin II formation. However, different ACEi seem to influence exercise-induced angiogenesis. The objective of this review was to investigate the effects of different ACEi on vessel growth in skeletal muscle induced by exercise training. The present study is characterized by a narrative literature review design, the databases of Scielo, Google Scholar and PubMed were consulted. There are different groups of ACEi , sulfhydryl group such as captopril and a carboxyl group such as perindiporil and enalapril that can influence their effects on ACE activity. It is already known that exercise promotes the increase of vessels from vessels already existing in the skeletal musculature, a process known as angiogenesis and contributes to the blood pressure reduction (BP). Although these different responses are still scarce, vessel endothelial growth factor (VEFG) and nitric oxide (NO) may participate. Thus, the use of different ACEi can influences the angiogenesis responses induced by exercise, being one of the important mechanisms for BP reduction. The choice of ACEi group should be carefully analyzed for hypertensive individuals who practice physical exercise. Keywords: Physical Education and Training. Microcirculation. Hypertension. ResumoOs inibidores da enzima conversora de angiotensina (iECA) são utilizados para redução da pressão arterial e resistência vascular modulando a atividade da ECA responsável pela formação da angiotensina II. Entretanto, diferentes iECAs parecem influenciar a angiogênese induzida pelo exercício físico. Desta maneira objetivo desta revisão foi investigar os efeitos de diferentes iECA sobre o crescimento de vasos no musculo esquelético induzido pelo exercício físico. O presente estudo caracteriza-se um delineamento de revisão de literatura narrativa, foram consultadas as bases de dados do Scielo, Google acadêmico e PubMed. Existem grupos distintos dos iECAs, grupo sulfidrila como o captopril e o grupo carboxila como o perindiporil e grupo que pode influenciar seus efeitos sobre a atividade da ECA. Já é sabido que O exrcício promove o aumento de vasos a partir de vasos já existentes na musculatura esquelética, processo conhecido como angiogênese e colabora para redução da pressão arterial (PA). Entretanto os iECAs parecem influenciar esta resposta do aumento da densidade capilar no músculo esquelético. Embora ainda sejam escassos estas diferentes respostas podem ter as participações do fator de crescimento endotelial de vasos (VEFG) e o óxido nítrico (NO). Desta maneira o uso dos grupos do iECAs podem influenciar as resposta da angiogênese induzido pelo exercício sendo um dos mecanismos importantes pela redução da PA. A escolha do grupo de iECA deve ser analisada com cautela para indivíduoS hipertensos que praticam exercício físico. Palavras-chave: Educação Física e Treinamento. Microcirculação. Hipertensão

Centella asiatica (L.) Urb. Prevents Hypertension and Protects the Heart in Chronic Nitric Oxide Deficiency Rat Model

Background: Hypertension is a major risk factor for cardiovascular disease (CVD), which is the number one cause of global mortality. The potential use of natural products to alleviate high blood pressure has been demonstrated to exert a cardioprotective effect. Centella asiatica (L.) Urb. belongs to the plant family Apiaceae (Umbelliferae). It contains a high amount of triterpenoid and flavonoid that have antioxidant properties and are involved in the renin-angiotensin-aldosterone system which is an important hormonal system for blood pressure regulation.Objective: This study aimed to investigate the effects of C. asiatica ethanolic extract on blood pressure and heart in a hypertensive rat model, which was induced using oral N(G)-nitro-l-arginine methyl ester (l-NAME).Methods: Male Sprague-Dawley rats were divided into five groups and were given different treatments for 8 weeks. Group 1 only received deionized water. Groups 2, 4, and 5 were given l-NAME (40 mg/kg, orally). Groups 4 and 5 concurrently received C. asiatica extract (500 mg/kg, orally) and captopril (5 mg/kg, orally), respectively. Group 3 only received C. asiatica extract (500 mg/kg body weight, orally). Systolic blood pressure (SBP) was measured at weeks 0, 4, and 8, while serum nitric oxide (NO) was measured at weeks 0 and 8. At necropsy, cardiac and aortic malondialdehyde (MDA) contents, cardiac angiotensin-converting enzyme (ACE) activity, and serum level of brain natriuretic peptide (BNP) were measured.Results: After 8 weeks, the administrations of C. asiatica extract and captopril showed significant (p < 0.05) effects on preventing the elevation of SBP, reducing the serum nitric oxide level, as well as increasing the cardiac and aortic MDA content, cardiac ACE activity, and serum brain natriuretic peptide level.Conclusion:C. asiatica extract can prevent the development of hypertension and cardiac damage induced by l-NAME, and these effects were comparable to captopril.

Exposure to a “safe” dose of environmental pollutant bisphenol A elevates oxidative stress and modulates vasoactive system in hypertensive rats

Due to the prevalence of hypertension (one of the major risk factors of CVD) in the population, it is necessary to explore the adverse effects of daily tolerable and “safe” dose of bisphenol A (BPA) under hypertensive conditions. The current study exposed the Nω-nitro-l-arginine methyl ester (L-NAME, 40 mg/kg b.w/day) induced hypertensive Wistar rats to BPA (50 μg/kg b.w/day) by oral administration along with appropriate controls for 30 days period. The results illustrate that a ‘safe’ dose of BPA does not influence the systolic blood pressure (SBP) and levels of circulatory biomarkers of tissue damage. On the other hand, BPA exposure significantly ( p < 0.05) elevates the thiobarbituric acid reactive substances (TBARS) content in plasma and tissues (heart, aorta, liver and kidney) in hypertensive rats when compared with respective control (BPA alone exposed) rats. Similarly, a significant modulation of ROS generation in RBC, plasma nitric oxide (NO) level and angiotensin-converting enzyme (ACE) activity was observed only under hypertensive milieu. In conclusion, the observed adverse effects during ‘safe’ dose of BPA exposure are specific to the hypertensive condition. Therefore, a precise investigation to explore the effects of BPA exposure in vulnerable hypertensive populations is highly suggested.

The Chemical Compounds of Flacourtia rukam Leaves and Their Inhibition of Angiotensin-converting Enzyme (ACE) Activity

Flacourtia rukam is a plant popular among people to treat hypertension, especially the Musi Banyuasin of south Sumatera, Indonesia. Isolation and identification of chemical compounds from F. rukam leaves and evaluation of their effects on antihypertensive activity have been conducted. Isolation of chemical compounds using chromatographic methods and identification using spectroscopic methods were compared with the reported data. The drug’s effects on antihypertension were determined using the angiotensin converting enzyme (ACE) inhibitory method. Two compounds were first reported and isolated from the leaves of F. rukam and identified as apigenin (1) and lupeol (2). These compounds were demonstrated to be effective in treating antihypertension with IC50 656.51 ± 1.55 µg/mL for apigenin and 15.12 ± 0.72 µg/mL for lupeol. It can be concluded that F. rukam leaves is a potential ACE inhibitor can be explored further as an effective antihypertensive agent.

Antihypertensive Peptides from Ultrafiltration and Fermentation of the Ricotta Cheese Exhausted Whey: Design and Characterization of a Functional Ricotta Cheese

Aiming at valorizing the ricotta cheese exhausted whey (RCEW), one of the most abundant by-products from the dairy industry, a biotechnological protocol to obtain bioactive peptides with angiotensin-I-converting enzyme (ACE)--inhibitory activity was set up. The approach was based on the combination of membrane filtration and fermentation. A Lactobacillus helveticus strain selected to be used as starter for the fermentation of the ultrafiltration protein-rich retentate (R-UF) obtained from RCEW. The fermented R-UF was characterized by a high anti-ACE activity. Peptides responsible for the bioactivity were purified and identified through nano-LC–ESI–MS/MS. The sequences identified in the purified active fractions of the fermented R-UF showed partial or complete overlapping with previously reported κ-casein antihypertensive fragments. The fermented R-UF was spray-dried and used to enrich ricotta cheese at different fortification level (1 and 5% w/w). An integrated approach including the assessment of the microbiological, chemical, functional, textural, and sensory properties was used to characterize the fortified products. A significantly higher anti-ACE activity was found in the ricotta cheese fortified with fermented R-UF as compared to the control and to the samples obtained with the unfermented R-UF fraction at the same levels of fortification. In particular, a 100 g portion of the ricotta cheese produced at 5% fortification level contained circa 30 mg of bioactive peptides. The fortification led to a moderate acidification, increased hardness and chewiness, and decreased the milk odor and taste of the ricotta cheese as compared to the control, while flavor persistence and sapidity improved.

Bradykinin and angiotensin-converting enzyme in serum of patients with diabetic retinopathy and the prognosis of diabetic macular edema development (pilot study)

BACKGROUND. Diabetic macular edema (DME) is a microvascular complication of diabetic retinopathy. One of the key roles in the pathogenesis of DME may belong to the components of rennin-angiotensin and kallikrein-kinin systems: bradykinin (Bk) and angiotensin-converting enzyme (ACE).PURPOSE. To determine the Bk and ACE concentration and ACE activity in serum of patients with proliferative diabetic retinopathy (PDR) and to estimate the significance of these parameters for the early diagnostic and prognosis of DMO.MATERIALS AND METHODS. Serum was collected from the 2 groups of patients with II type diabetes. Group I (n=9) had DME, group II (n=27) had PDR without DME. Control group (n=14) consisted of adult volonteers without diabetes and ophthalmic diseases. Concentration of Bk and ACE was measured using ELISA kits, ACE activity was determined enzymatically with specific fluorogenic substrate.RESULTS. Concentration of Bk in serum of patients without DME did not differ from one in controls (12,00 (9,70; 12,40) pg/ml) while all patients with DME had Bk level of 14,69 (13,68; 16,78) pg/ml that was significantly higher (p<0,01). In patients without DME ACE concentration (88,60 (77,30; 97,45) ng/ml) and ACE activity (6,8 (5,1;7,1) nmol/min·ml) were higher than normal (p<0,01) while in the case of DME concentration of ACE increased (77,36 (70,24; 86,29 ng/ml, p<0,01) and activity remained normal. The Bk/ACE concentrations ratio decreased in patients without DME and increased in those having DME.CONCLUSION. Patients with DME have increased Bk concentration along with nearly normal ACE concentration that indicate predominance of Bk synthesis over its degradation that may lead to the DME development. The Bk/ACE ratio decrease in patients with uncomplicated PDR and increase significantly in ones with DME. It means that determination of Bk in serum of patients with PDR may be used for the prediction of DME development. The Bk/ACE concentrations ratio may be even more informative.

Effects of camel milk hydrolysate on blood pressure and biochemical parameters in fructose-induced hypertensive rats

Purpose This study aims to investigate the antihypertensive effect of camel milk hydrolysate in rats with fructose-induced hypertension. Design/methodology/approach The antihypertensive effect of fermented camel milk was determined using 6 groups comprising 36 Wistar male rats. Blood pressure of rats was altered via exposure to a 10% fructose (w/v) diet in drinking water for 3 weeks before conducting 21 days of treatment. The authors conducted the experiment for short and long term using different doses of 800 and 1,200 mg/kg body weight. Serum was used to assay total cholesterol (TC), triglyceride (TG), glucose and insulin levels using standard biochemical kits. Findings The group that received 1,200 mg hydrolysate camel milk (HM) has significantly (p = 0.003) reduced systolic and diastolic blood pressure after a short exposure time (4–8 h). These effects were significantly (p = 0.005) comparable to the nifedipine (NIF) drug group. Similar long-term (21 days) effects on blood pressure were observed in 1,200 mg HM and NIF groups. Angiotensin-converting enzyme (ACE) activity and levels were also reduced in a correlation with blood pressure reduction only in HM1200 and HM800 treated groups. The authors observed no significant effect on blood pressure in groups receiving the 800 mg HM or 1,200 mg unhydrolyzed camel milk (UM). Rats receiving the 10% fructose diet showed significant differences from control rats regarding their blood biochemistry, including TG, TC, blood glucose and insulin levels. Rats in groups NIF, HM1200 and HM800 showed a significant (p < 0.05) reduction in serum glucose, insulin, TG and TC levels toward the baseline level. Research limitations/implications Further mechanistic investigation on the HM antihypertensive activity is highly recommended before suggesting HM as a product to reduce blood pressure. While drug–food interaction between HM and antihypertensive drugs, especially ACE inhibitors, is probable, UM seems not to affect blood pressure or ACE activity and therefore is expected to have no or minimal effects on the activity of other antihypertensive drugs. Investigation of ACE expression from various organs including lungs and leukocytes is highly recommended in future works using sodium dodecyl-sulfate polyacrylamide gel electrophoresis and western blot analysis or reverse transcription polymerase chain reaction. Originality/value No previous studies have measured the antihypertensive activity of milk hydrolysate mediated by the reduction of ACE activity and levels in plasma. Mechanisms involved in attenuating the levels of ACE warrant further investigation.

Impact of Lipid Profile, Cardiac Biomarkers, Serum Angiotensin-Converting Enzyme Activity, Oxidative Stress and Antioxidant on Blood Pressure Status

The hemodynamic determinants of myocardial oxygen demand measured were heart rate (HR), systolic blood pressure (BP), and rate pressure product (RPP). This study aimed to evaluate the impact of lipid profile, cardiac biomarkers, and serum angiotensin-converting enzyme (ACE) activity, oxidative stress (plasma malondialdehyde, MDA; conjugated diene, DC), and antioxidant status (glutathione peroxidase, GPx) on BP. Three hundred and six non-ST-elevated myocardial infarction (NSTEMI) patients compared to 410 healthy controls. The diastolic and systolic BP was correlated positively with serum ACE activity. The rate pressure product (RPP) was correlated negatively with Fasting glucose (r= -0.144; p = 0.012), HbA1c (r= -0.117; p = 0.041) and GPx activity (r= -0.148; p = 0.009), and positively with smoking (r = 0,197; p = 0.001), BMI (r = 0,219; p = 0.001), peak cTnI (r = 0.131; p = 0.022), serum ACE activity (r = 0,190; p = 0.001) and DC level (r = 0.189; p = 0.001) in NSTEMI patients. Regarding healthy controls, no correlation was found between the diastolic or systolic BP with serum ACE activity, peak cTnI, MDA, DC level, GPx activity, and lipid parameters. The existence of a specific correlation between the rate pressure product, diastolic and systolic BP and, lipid profile, serum ACE activity and, cardiac biomarkers, oxidative stress, and antioxidant status increase the NSTEMI risk on patients.