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OBJECTIVE@#To investigate the effect of ANP32A silencing on invasion and migration of colon cancer cells and the influence of the activity of AKT signaling pathway on this effect.@*METHODS@#Colorectal cancer HCT116 and SW480 were transfected with a small interfering RNA targeting ANP32A via a lentiviral vector. At 24, 48 and 72 h after the transfection, the changes in cell proliferation and AKT activity in the cells were detected using MTT assay and Western blotting, respectively. HCT116 and SW480 cells were treated with the AKT agonist SC79 or its inhibitor MK2206 for 24, 48, 72 and 96 h, and the changes in cell migration and invasion ability were analyzed using Transwell chamber assay and cell proliferation was assessed using MTT assay. The effects of SC79 and MK2206 on migration and invasion abilities of HCT116 and SW480 cells with or without ANP32A silencing were examined using wound healing and Transwell chamber assays, and the changes in the expression of metadherin (MTDH), a factor associated with cells invasion and migration, was detected with Western blotting.@*RESULTS@#Lentivirus-mediated ANP32A silencing significantly down-regulated the activity of AKT and inhibited the proliferation of both HCT116 and SW480 cells (P < 0.01). The application of AKT inhibitor MK2206 obviously inhibited the proliferation, invasion and migration of the colorectal cancer cells (P < 0.05), while the AKT agonist SC79 significantly promoted the invasion and migration of the cells (P < 0.01). In HCT116 and SW480 cells with ANP32A silencing, treatment with MK2206 strongly enhanced the inhibitory effects of ANP32A silencing on cell invasion and migration (P < 0.05) and the expression of MTDH, while SC79 partially reversed these inhibitory effects (P < 0.01).@*CONCLUSION@#ANP32A silencing inhibits invasion and migration of colorectal cancer cells possibly by inhibiting the activation of the AKT signaling pathway.
Subject(s)
Humans , Proto-Oncogene Proteins c-akt , Cell Proliferation , Blotting, Western , Cell Movement , Colonic Neoplasms , Membrane Proteins , RNA-Binding Proteins/genetics , Nuclear ProteinsABSTRACT
OBJECTIVE@#To compare the effects on the heart rate variability (HRV) and the expression of the atrial natriuretic peptide (ANP) in the model rats of irritable bowel syndrome with predominant diarrhea (IBS-D) rats complicated with anxiety between moxibustion of "biaoben acupoint combination" and that of "conventional acupoint combination".@*METHODS@#Of 50 healthy SPF female SD rats, aged 3 months, 8 rats were selected randomly as a blank group, and the rest rats were prepared to be the model of IBS-D complicated with anxiety. Twenty-four rats after successfully modeled were randomized into a model group, a conventional acupoint combination group (convention group) and a biaoben acupoint combination group (biaoben group), 8 rats in each one. In the convention group, moxibustion was delivered at "Tianshu" (ST 25), "Zusanli"(ST 36) and "Shangjuxu"(ST 37); and in the biaoben group, moxibustion was applied to "Neiguan" (PC 6), "Zusanli" (ST 36), and "Guanyuan" (CV 4). One session of moxibustion took 20 min, once daily, for 14 days in total. Before and after intervention, the body mass and fecal moisture content were compared in the rats of each group; using abdominal wall withdrawal reflex, the visceral hypersensitivity was evaluated; with elevated plus maze (EPM) and light-dark box (LDB), the anxiety conditions were assessed. After intervention, HRV was compared among groups, the ultrastructure of intestinal mucosa was observed under the transmission electron microscope in the rats of each group, and ANP expression in the myocardial tissue was detected using Western blot method and immunofluorescence.@*RESULTS@#Before the intervention, compared with the blank group, the body mass and visceral pain threshold of rats were reduced in the model group, the convention group and the biaoben group (P<0.05), fecal moisture content and AWR scores (at the dilatation pressure of 40, 60 and 80 mm Hg, 1 mm Hg ≈ 0.133 kPa) were elevated (P<0.05); and time in the open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were decreased (P<0.05). After the intervention, compared with the blank group, in the model group, the body mass, visceral pain threshold, standard diviation of NN intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) were dropped (P<0.05), fecal moisture content, AWR scores (the dilation pressures of 40, 60 and 80 mm Hg), LF/HF and ANP expression were increased (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were decreased (P<0.05). When compared with the model group, in the convention group and the biaoben group, the body mass, visceral pain threshold, SDNN and RMSSD were increased (P<0.05), fecal moisture content, AWR scores (the dilation pressures of 60 and 80 mm Hg), LF/HF and ANP expression were dropped (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were increased (P<0.05). In the biaoben group, compared with the convention group, the body mass, visceral pain threshold, SDNN and RMSSD were elevated (P<0.05), fecal moisture content, AWR score (the dilation pressure of 80 mm Hg), LF/HF and ANP expression were decreased (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were increased (P<0.05). The epithelial cells of the intestinal mucosa showed a normal morphology in the blank group, the tight junction of the cells was disrupted and the junction was loose in the model group; the tight junction was imperfect in the convention group, but it was intact in the biaoben group.@*CONCLUSION@#Compared with the conventional acupoint combination, moxibustion of biaoben acupoint combination is more effective on the symptoms of IBS-D complicated with anxiety in the model rats. The effect mechanism may be related to attenuating anxiety-like negative emotions, positively regulating HRV, stabilizing IBS-D intestinal mucosal barrier and down-regulating the expression of ANP in myocardium.
Subject(s)
Rats , Female , Animals , Irritable Bowel Syndrome/therapy , Rats, Sprague-Dawley , Moxibustion/methods , Heart Rate , Atrial Natriuretic Factor , Acupuncture Points , Anxiety/therapyABSTRACT
The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced cardiac hypertrophy and facilitated the development of cardiac hypertrophy. BRD4 was involved in the prohypertrophic effect of PARP1, as implied by the observations that BRD4 inhibition or silencing reversed PARP1-induced hypertrophic responses, and that BRD4 overexpression suppressed the anti-hypertrophic effect of PARP1 inhibitors. Interactions of BRD4 and PARP1 were observed by co-immunoprecipitation and immunofluorescence. PARylation of BRD4 induced by PARP1 was investigated by PARylation assays. In response to hypertrophic stimuli like ISO, PARylation level of BRD4 was elevated, along with enhanced interactions between BRD4 and PARP1. By investigating the PARylation of truncation mutants of BRD4, the C-terminal domain (CTD) was identified as the PARylation modification sites of BRD4. PARylation of BRD4 facilitated its binding to the transcription start sites (TSS) of hypertrophic genes, resulting in enhanced phosphorylation of RNA Pol II and transcription activation of hypertrophic genes. The present findings suggest that strategies targeting inhibition of PARP1-BRD4 might have therapeutic potential for pathological cardiac hypertrophy.
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Background: Hydrochloric acid (pH 1.5-3.5) being the major component of gastric acid is produced by parietal cells of stomach. Its secretion is a complex and relatively energetically expensive process. The preservation of acidity of stomach is evidently important because of its implications in peptic and duodenal ulceration.Methods: In the present study, we attempted to compare the activity of 13 (F1-F13) antacid formulations (5-liquid, 4- quick releases and 4- tablets) by using acid-base neutralization studies. Preliminary antacid test (PAT) was performed to define whether the given formulation falls under the category of antacid wherein the pH of the antacid-acid (HCl) solution should be higher than pH of 3.5. The chosen antacids were further subjected to acid neutralizing capacity (ANC) (reaction between the sample of antacid and amount of acid neutralized by the formulation) and acid neutralizing potential (ANP) which explains the time duration during which a given sample of antacid can maintain pH above 3.5).Results: Out of the 13 samples tested, two formulations of pastels (F6, F12) were rejected as per the standard protocol of classifying formulations as antacids after screening for PAT. Sample F5 was found to have the highest ANC. F7 also showed highest ANC among the tablets tested. Also, F13 showed better ANC and ANP as in comparison to other quick releases.Conclusions: Digene products (F5, F7, and F13) showed better antacid properties. This data would provide insights into development of drug, comparison between antacids depending on their chemical formulation and determination of dosage to avoid plausible side effects.
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Introduction: CECT is very accurate and sensitiveinvestigation in evaluating the severity of acute pancreatitisand the associated complications.With the help of CT, wecan manage the patient of acute pancreatitis by categorisingthem into mild, moderate and severe cases according tomodified CT severity index and predict the clinical outcomeas well. CT mainly detects the associated complication suchas sterile or necrotic fluid collection, pseudocyst fomation,walled off necrosis, pleural effusion, liver cirrhosis mainlyin chronic alcoholic patients vascular complications at earlystage.Aim: To study the role of computed tomography in predictingseverity of acute pancreatitis and its correlation with clinicaloutcome.Material and Methods: The Study was carried out atDepartment of Radio Diagnosis, Krishna Institute of MedicalScience, Karad, Maharashtraamong 46 cases of acutepancreatitis.Result: The mean age of participants in the present study wasobserved to be 35.95 years. Majority were males (39, 84.78%)and 7 were females (15.22%), with male: female ratio of 1:0.18.The majority of the cases (78.29%) were alcoholic while 10cases were non alcoholic. Cases associated with Gall stoneswere21.73% 95.65% cases presented with abdominal pain.Based on Computed Tomography (CT) findings, we found63% patients with acute interstitial edematous pancreatitis and37% patients with acute necrotic pancreatitis among 46 cases.When we evaluated Modified CT Severity index among thestudy cases, we observed that 19.56% cases have mild index,majority (56.52% cases) have moderate index while 23.91%cases have severe index. We also found that majority ofpercentage of cases clinically cured and discharged i.e. 47.82%. 19.56% of the total study subjects reported recurrence ofepisodes of pancreatitis, while 30.43% of the total patientsturned into chronic pancreatitis.Conclusion: Computed tomography can be used to knowthe extent of disease within pancreatic parenchyma andto diagnose associated complications, at early stage.It canassess severity of acute pancreatitis and forecast progress ofpancreatitis.
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Objective: To compare the influences of Shenfu Qiangxin Pillsat different medication time and dosage on corpulmonale model rats, and define the best drug use entry point of Shenfu Qiangxin Pills in rats with corpulmonale. Methods: The smudging combined with ip rattlebush alkaline were used to prepare rats corpulmonale model, and the effects of Shenfu Qiangxin Pills at different drug administration time and dosage on right ventricle hypertrophy index, alveolar mean linear intercept, alveolar numbers, airway inflammation pathological scores, and matrix metalloproteinase-9 (MMP-9) in rats were investigated. Results: Comparing with the model group, the right ventricle hypertrophy index of rats in high- and low-dosage groups of Shenfu Qiangxin Pills was significantly reduced. Alveolar number was significantly increased. Serum ANP level was reduced. Cardiopulmonary MMP-9 level was reduced (P < 0.05). The effects in the high-dosage group was significant. Conclusion: The short-term drug administration of Shenfu Qiangxin Pills for two weeks was superior to long-term precaution drug administration for four weeks by reducing right ventricle hypertrophy index and inhibiting airway reaction, and existed dose-effect relationship.
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Objective To study the effect of atrial natriuretic peptide(ANP)deletion on melanoma growth. Methods A subcutaneous xenotransplanted melanoma model was established in ANP knockout mice and C57BL/6J mice. The tumor volume was measured at the sixth day after establishment of the subcutaneous transplantation. Tumor cell proliferation and tumor-induced angiogenesis were detected by immunohistochemical staining. Results The volume and weight of xenotransplanted melanoma were significantly decreased in the ANP knockout mice compared with those in the C57BL/6J mice. The proliferative tumor cells and microvessel density were significantly decreased in the tumor tissues of ANP knockout mice compared with those in the C57BL/6J mice. Conclusions ANP deletion significantly suppresses xenotransplanted melanoma growth through inhibiting the tumor cell proliferation and angiogenesis.
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Objective To investigate the role of atrial natriuretic peptide (ANP) in lung metastasis of melanoma. Methods Melanoma B16F10 cells were intravenously injected into ANP knockout mice and C57BL/6J mice. After three weeks, the mice were sacrificed, and the lungs were removed, embedded, and examined by pathology using HE staining. The numbers of metastatic foci on the lung surface and micrometastatic foci in the lung tissues were counted. Results The ANP knockout mice displayed fewer metastatic foci on the lung surface and less micrometastatic foci in the lung tissues of ANP knockout mice than in the C57BL/6J mice. Conclusions ANP deletion significantly suppresses the metastasis of melanoma in the lung of mice.
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To study the effect and mechanism of Dendrobium candidum on isoproterenol-induced myocardial hypertrophy in rats, 60 healthy SD rats(30 males and 30 females) were randomly divided into 5 groups(12 in each group): normal group, model group, three D. candidum preventive administration groups(0.09, 0.18, 1.1 g·kg⁻¹). Except for the normal group, rats of other groups were injected back subcutaneously with ISO(5 mg·kg⁻¹) for 10 consecutive days. At the same time, preventive administration groups began to give different doses of the sample for 30 days and model group began to give normal saline. Left ventricular systolic pressure(LVSP) was measured in each group by common carotid artery cannulation, and the left ventricle(LW)/tibia length, heart weight index(HWI) and myocardial hydroxyproline(Hydro) content were calculated. Myocardial tissue HE staining and Masson staining were used to observe the myocardial structure and the degree of myocardial fibrosis respectively. Atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), and cardiac troponin I(cTN-I) concentration were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that as compared with the normal group, the levels of ANP, BNP and cTN-I in plasma were significantly increased in ISO-induced hypertrophic rats; as compared with the model group, D. candidumcan inhibit ISO-induced ventricular pressure and ventricular hypertrophy, reduce myocardial collagen synthesis, improve myocardial fibrosis and ventricular remodeling, and significantly down-regulate ANP, BNP and cTN-I levels in plasma. This study shows that D. candidum has a protective effect on isoproterenol-induced cardiac hypertrophy.
Subject(s)
Animals , Female , Male , Rats , Cardiomegaly , Drug Therapy , Dendrobium , Chemistry , Drugs, Chinese Herbal , Pharmacology , Isoproterenol , Myocardium , Pathology , Rats, Sprague-DawleyABSTRACT
ABSTRACT For combustion engines to perform well, it is necessary that the fuel used be of high quality. Fuel quality can be analyzed through different physicochemical properties. This study presents comparisons between the values presented in literature, legislation and those obtained through experimental tests of different biodiesel samples. Biodiesel is a promising alternative of renewable energy obtained from raw material. The properties observed in this study are: Viscosity, density, cloud point, pour point and calorific value. The data explored by this work aims to bring solidification to the methodologies and equipment necessary for a better characterization of biodiesel.
Subject(s)
Plant Oils , Biofuels , Renewable Energy , Natural GasABSTRACT
Tinnitus is recognized as a refractory disease, which is common in clinic, and always treated from the liver and kidney. We treat tinnitus mainly by heart based on syndrome differentiation. It often works well when the leftpulse is abnormal. Referring to ancient literature, we find that the heart is related to ears by meridians, and the kidney and heart govern ears. The normal function of heart and kidney means normal hearing. The heart secretes atrial natriuretic polypeptins (ANP), whose receptor is widely distributed in ears and can increase the cochlear blood flow. In this paper we explore the relationship between the heart and the ears so as to provide theories of treatment by heart for tinnitus.
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Aim To examine the effect of Nampt over-expression on cardiac hypertrophy,and elucidate the role of NF-κB.Methods The cultured neonatal car-diomyocytes were pretreated with 100 μmol · L-1 PE or transfected with Nampt.The mRNA and protein ex-pression of Nampt were determined by Real-time PCR and Western blot respectively.The cardiomyocyte hy-pertrophy was monitored by measuring cell-surface area and the mRNA levels of ANP and BNP,which were biomarkers of hypertrophic response.Moreover,we te-sted the effects of Nampt on NF-κB-dependent tran-scription activity through luciferase reporter gene as-says.Results Nampt overexpression significantly in-creased cardiomyocyte surface area and the mRNA ex-pression of ANP and BNP.In addition,Nampt overex-pression could markedly increase NF-κB-dependent transcription activity. Moreover, when p65 was knocked down,cardiomyocytes with Nampt overexpres-sion could not induce cardiac hypertrophy.Conclusion Overexpression of Nampt induces cardiac hypertro-phy by increasing NF-κB-dependent transcription activ-ity.
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Aim To explore the differences in hyper-trophic marker genes such as atrial natriuretic peptide ( ANP) , brain natriuretic peptide ( BNP) and β-myo-sin heavy chain (β-MHC) genes in different models of cardiac hypertrophy. Methods Respectively using re-nal abdominal aortic coarctation ( AAC) , arteriovenous fistula ( AVF) and isoproterenol ( ISO) methods to es-tablish C57BL/6 mouse model of cardiac hypertrophy. After modeling, each mouse ’ s body weight ( BW ) , heart weight ( HW) and left ventricular weight ( LVW) were weighed, and the heart weight ( HW/BW) and left ventricular index ( LVW/BW ) were calculated;myocardium by HE staining, pathological morphologi-cal changes were observed; myocardium by immuno-histochemistry, ANP, BNP and β-MHC protein ex-pression was observed;myocardium by Real-time PCR detection, ANP, BNP and β-MHC mRNA expression was observed. Results Compared with control group, HW/BW and LVW/BW were increased in three mod-els. Through the light microscope, each mouse model showed varying degrees of cardiac hypertrophy. ANP, BNP and β-MHC were increased in the protein and mRNA expression. Compared with AAC group, AVF and ISO groups’ myocardial tissue ANP, BNP and β-MHC expression were decreased in the protein and mRNA expression. Conclusions Three cardiac hy-pertrophy models are successful. Cardiac tissue ANP, BNP and β-MHC expression in AAC model exceeds AVF and ISO model.
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Objective:To study the antihypertensive effect of the extract from compound Prunella vulgaris L. in spontaneous hy-pertension(SH)rats. Methods:Forty SH rats were randomly divided into the model group,high,middle and low dose groups of ex-tract from vompound Prunella vulgaris L. ,the compound kendir leaves tablets Ⅰ group with 8 ones in each. Non-invasive blood pres-sure measurement was used to detect the SBP and DBP of the SHR rats. Then the serum NO,AngⅡ ,ET-1 and ANP content were measured after the eight-week treatment. The pathological changes were observed after kidney HE staining in the SH rats. Results:Compared with that in the model group,the blood pressure in high-dose treatment group,middle-dose treatment group and the positive model group was significantly decreased(P < 0. 05). The AngⅡ and ET-1 levels in high-dose treatment group,middle-dose treatment group and the positive model group were decreased(P < 0. 01),and NO and ANP contents in serum were significantly increased when compared with those in the model group(P < 0. 01). The pathological examination showed that the pathological changes in the model group were faster than those in all the drug-treatment groups,the pathological changes included glomerular and renal tubular atrophy, glomerular vascular wall thickening and renal tubular epithelial cell degeneration or necrosis. Conclusion:The extract from compound Prunella vulgaris L. can reduce blood pressure of SH rats. The mechanism may be associated with the level reduction of AngII and ET-1 and content elevation of NO and ANP.
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Various nutritional supplements (herbs, vitamins, and micronutrients) improve responses and adaptations to resistance exercise. ANP is a heart hormone that contributes to fluid, electrolyte and blood pressure homeostasis through its natriuretic and vasodilative actions. In the present study, the adaptation of ANP in response to resistance exercise was investigated in rats supplemented with glutamine for five weeks. The results showed that supplementation with glutamine did not influence the number of ANP granules per atrial cardiocyte in sedentary animals. In exercised-trained rats, the number and diameter of the granules was significantly higher in comparison with the control group and in exercised animals supplemented with glutamine there was significant increase in the number and diameter of ANP granules compared with controls. Altogether, these data indicated that in resistance exercise rats, glutamine significantly enhances cardiac ANP thus implicating the beneficial effects of glutamine supplementation to the ANP system.
Vários suplementos nutricionais (ervas, vitaminas e micronutrientes) melhoram as respostas e adaptações ao exercício resistido. O ANP é um hormônio cardíaco que contribui para a homeostase de líquidos, eletrólitos e controle da pressão arterial através de suas ações natriurética e vasodilatadora. No presente estudo, a adaptação do ANP em resposta ao treinamento resistido foi investigada em ratos suplementados com glutamina durante cinco semanas. Os resultados mostraram que a suplementação com glutamina não influenciou o número de grânulos de ANP por cardiomiócito em animais sedentários. Em ratos treinados, o número e o diâmetro dos grânulos foi significativamente maior em comparação com o grupo controle e nos animais treinados e suplementados com glutamina houve um aumento significativo no número e diâmetro dos grânulos de ANP comparativamente com os controles. Em conjunto, estes dados indicam que, nos ratos submetidos ao treinamento resistido, a glutamina aumentou significativamente os níveis de ANP cardíaco, mostrando assim, os efeitos benéficos da suplementação com glutamina para o sistema de ANP.
Varios suplementos nutricionales (hierbas, vitaminas y micronutrientes) mejoran las respuestas y adaptaciones al ejercicio de resistencia. El ANP es una hormona cardíaca que contribuye a la homeostasis de fluidos, electrolitos y de control de la presión arterial a través de sus acciones vasodilatadora y natriurética. En el presente estudio, se investigó la adaptación de la ANP en respuesta al entrenamiento de resistencia en ratones suplementados con glutamina durante cinco semanas. Los resultados mostraron que la suplementación de glutamina no influyó en el número de gránulos de ANP por cardiomiocito en animales sedentarios. En ratas entrenadas, el número y el diámetro de los gránulos fue significativamente mayor en comparación con el grupo control y en los animales entrenados y suplementados con glutamina hubo un aumento significativo en el número y diámetro de los gránulos de ANP en comparación con los controles. En conjunto, estos datos indican que en ratones sometidos a entrenamiento de resistencia, la glutamina aumentó significativamente el nivel de ANP cardiaco mostrando de esta manera los efectos beneficiosos de la administración de glutamina para el sistema de ANP.
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Among the topics studied in physiology and aging, a hormone has been drawing attention from the scientificcommunity: the Atrial Natriuretic Peptide (ANP). The ANP, which is produced by the cardiac atria, hasdemonstrated decisive action in endocrine mechanisms of action inhibiting sodium reabsorption in nephrons,revealing a direct influence on physiological mechanisms linked to aging and chronic stress.The overall objectiveof this study was to assess and analyze scientific literature on the ANP in the Pubmed database from 2010 to2012. 30 articles were collected, verifying authorship and gender division of species, instruments and typesof research. The results showed that the research of multiple authorship appeared mostly with 99.1%, being51.8% of male authorship, 17.9% of female authorship and 29.5% of publications not identified. Researchwith only one author appears with 0.8% in total. As the types of species used, it was observed 50.3% of theworks with humans, 40% with animals and 6.7% mixed (animal / human). As to the instruments used, thebiochemical markers were the ones that stood out, with 30%, followed by label arterial pressure with 12, 2%,drugs, with 11.1% and microscopic studies with 10%. In the typology of research, biochemical research appearsfirst, with 33.3%, followed by research morphophysiological/biochemical research, with 30%, Physiological/ biochemical, with 26.7%, Physiological with 6.7% and Morphophysiological with 3.3%. We can concludethat the publications about the hormone ANP are still little explored when the focus is aging. In the analyzedpublications, there is important information about the physiological and biochemical role of ANP as well ason their molecular composition.
Subject(s)
Humans , Male , Female , Cardiovascular Diseases/physiopathology , Aging/physiology , Atrial Natriuretic Factor/physiology , Kidney DiseasesABSTRACT
Atrial natriuretic peptide (ANP) a powerful vasodilator, and a protein (28-amino acid peptide) hormone secreted by heart muscle cells. It is released in response to atrial distention, stretching of the vessel walls, sympathetic stimulation of β-adrenoceptors, raised sodium concentration, angiotensin-II and endothelin. ANP binds to three cell surface receptors called ANP receptors. The overall effect of ANP on the body is to counter increases in blood pressure and volume caused by the renin-angiotensin system. It has also been reported to increase the release of free fatty acids from adipose tissue. Regulation of its effects is achieved through gradual degradation of the peptide by the enzyme neutral endopeptidase (NEP). Inhibitors of NEP are currently being developed to treat disorders ranging from hypertension to heart failure. Synthetic analogs of ANP have been investigated as potential therapies for the treat-ment of decompensated heart failure and other diseases.
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Atrial natriuretic peptide (ANP) a powerful vasodilator, and a protein (28-amino acid peptide) hormone secreted by heart muscle cells. It is released in response to atrial distention, stretching of the vessel walls, sympathetic stimulation of β-adrenoceptors, raised sodium concentration, angiotensin-II and endothelin. ANP binds to three cell surface receptors called ANP receptors. The overall effect of ANP on the body is to counter increases in blood pressure and volume caused by the renin-angiotensin system. It has also been reported to increase the release of free fatty acids from adipose tissue. Regulation of its effects is achieved through gradual degradation of the peptide by the enzyme neutral endopeptidase (NEP). Inhibitors of NEP are currently being developed to treat disorders ranging from hypertension to heart failure. Synthetic analogs of ANP have been investigated as potential therapies for the treat-ment of decompensated heart failure and other diseases.
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Durante el desarrollo de la hipertensión arterial, las interacciones entre las sobrecargas de presión y de volumen conducen a diferentes patrones de hipertrofia cardíaca y a un aumento de los péptidos natriuréticos (PN). Los perfiles de síntesis y secreción de ANP y BNP se han investigado en modelos de hipertensión arterial; sin embargo, aún no se ha estudiado la evolución diferencial de estos perfiles durante períodos agudos y crónicos de la hipertrofia cardíaca producida por sobrecarga de volumen. Por este motivo estudiamos ratas Sprague- Dawley con el modelo DOCA-sal a las 2, 4, 6 y 12 semanas, correlacionando la evolución de dichos perfiles con la hipertrofia cardíaca y la hipertensión arterial. El grado de hipertrofia cardíaca se correlacionó positivamente con la expresión del ANP en el ventrículo izquierdo y con los niveles de ANP en plasma. La expresión del ANP aumentó a las 4 semanas de tratamiento, mientras que la de BNP se incrementó recién a las 6 semanas. Asimismo, el BNP plasmático se incrementó sólo en el grupo con 12 semanas de tratamiento, mientras que el ANP plasmático mostró un aumento a partir de las 2 semanas de tratamiento. Durante el desarrollo de la hipertrofia cardíaca producida en el modelo DOCA-sal, la síntesis y la secreción de los PN responden en forma diferencial, con incremento precoz del ANP. Además, el aumento de éste superó al de BNP en todos los grupos DOCA-sal, lo que permitiría considerar al ANP como un marcador más específico de la sobrecarga de volumen.
The interactions between pressure and volume overload that occur in hypertension lead to different patterns of cardiac hypertrophy and to increase in natriuretic peptides (NPs). The profiles of ANP and BNP synthesis and secretion have been investigated in models of hypertension; however, the different evolution of these profiles during the acute and chronic periods of pressure overload-induced cardiac hypertrophy is still unknown. For this reason, we studied DOCA-salt treated Sprague-Dawley rats at weeks 2, 4, 6 and 12 and correlated the evolution of these profiles with cardiac hypertrophy and hypertension. Cardiac hypertrophy had a positive correlation with ANP expression in the left ventricle and with ANP plasma levels. BNP expression increased after 4 weeks of treatment while ANP increased significantly after 6 weeks. In addition, BNP plasma levels increased only in the group treated for 12 weeks, while ANP plasma levels increased from week 2. NP secretion has a differential response in the early stages of the development of cardiac hypertrophy induced by the DOCA-salt model, with an early increase in ANP. As ANP levels were exceeded to those of BNP in all the DOCA-salt groups, ANP might be considered a more specific marker of volume overload.
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Objective To investigate the effect of acute exhausted exercise in high temperature environment on the expression of myocardial HSP70 and plasma ANP level of in rats. Methods Forty eight male Sprague-Dawley rats was randomly and equally assigned to the following six groups:control group(C),exercise group(E),one-hour heat exposure group (H), heat exposure and exercise group (HE), exercise and 24 hours after exercise group(E'),heat exposure and 24 hours after exercise(HE'). Each group consisted of 8 rats. Rats in E,HE,E' and HE' ran on a treadmill until exhaustion, while rats in H and H' were exposed in a high temperature environment (33℃ ,50%RH) for one hour. Rats in C,E,HE and H were killed immediately after exercise or heat exposure. Rats in HE' and E' were killed 24 hours after exercise. Samples from myocardium and serum were collected for determining HSP70,ANP and CK-MB. Results(1) HSP70 levels in groups E and E' are significantly higher than that in group C(P<0.05 and P<0.01,respectively),and the level in group HE' is significantly higher than that in groups H and E'(P<0.01 );The HSP70 level in group H is significantly higher than that in group C. (2) The ANP and CK-MB levels in group E are Significantly higher than that in group C.and in group HE is higher than in group H (P<0.05);The HSP70 levels in group E' and HE' significantly decrease comparing to that in groups E and HE (P<0.01). Conclusions(1)Both heat exposure and exercise can induce the increased expression of myocardial HSP70 in rats and the peak expression is seen 24 hours after exercise. The increased expression of HSP70 may have protective effects on the heat-induced myocardial injury. (2) The increased ANP levels in plasma immediately after exhausted exercise improves the blood circulation in myocardium and hints the potential possibility of myocardial damage. However,the high temperature environment does not strengthen the increase of plasma ANP level that caused by exhaustive exercise.