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1.
Article in Chinese | WPRIM | ID: wpr-878930

ABSTRACT

The present study is to investigate the absorption characteristics of the main components in Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats with everted intestinal sac models. Intestinal sac fluid samples were collected in different part of intestine(duodenum, jejunum, ileum, colon) at different time after administration of different concentration of P. orientale extract(5.0,10.0, 20.0 mg·mL~(-1)). An UPLC-TQD method was employed for the determination of six components including orientin, isoorientin, vitexin, protocatechuic acid, kaempferol-3-O-β-D-glucoside and quercitrin in the intestinal sac samples. The absorption rate and cumulative absorption were calculated to analyze the intestinal absorption characteristics of six components in normal and myocardial ischemia model rats. The P-glycoprotein(P-gp) inhibitor was applied to investigate influence of intestinal absorption of six components in P. orientale extract. The results showed that the main absorption sites were concentrated on the duodenum at low concentration, while they were the colon at the medium concentration and the ileum at high concentration in control groups. In the condition of myocardial ischemia model, the main absorption sites focus on the ileum and jejunum at low concentration; the main absorption sites were in the ileum at the medium concentration and main absorption sites were the duodenum and ileum at high concentration. Compared with the normal group, the absorption rate and cumulative absorption of the six components significantly decreased in the model group. P-gp inhibitor markedly increased the absorption rate and cumulative absorption of six components in the model group, inferring that the 6 components may be the substrates of P-gp, and the mechanism needs further study. In this study, it is revealed that the six components of P. orientale extract can be absorbed into the intestinal sac, and it is an effective method to assess the intestinal absorption characteristics of P. orientale extract through everted intestinal sac model, providing data support for the clinical application and further development of P. orientale.


Subject(s)
Animals , Intestinal Absorption , Intestines , Isoproterenol , Myocardial Ischemia/chemically induced , Polygonum , Rats , Rats, Sprague-Dawley
2.
Braz. j. med. biol. res ; 53(2): e8793, 2020. tab, graf
Article in English | LILACS | ID: biblio-1055493

ABSTRACT

Aliskiren (ALS) is well known for its antihypertensive properties. However, the potential underlying the molecular mechanism and the anti-hypertrophic effect of ALS have not yet been fully elucidated. The aim of the present study was to investigate the role of ALS in mammalian target of rapamycin (mTOR) and apoptosis signaling using in vivo and in vitro models of cardiac hypertrophy. A rat model of cardiac hypertrophy was induced by isoproterenol treatment (5 mg·kg-1·day-1) for 4 weeks, with or without ALS treatment at 20 mg·kg-1·day-1. The expression of hypertrophic, fibrotic, and apoptotic markers was determined by RT-qPCR. The protein expression of apoptotic markers mTOR and p-mTOR was assessed by western blot analysis. The proliferation of H9C2 cells was monitored using the MTS assay. Cell apoptosis was analyzed using flow cytometry. In vivo, isoproterenol-treated rats exhibited worse cardiac function, whereas ALS treatment reversed these dysfunctions, which were associated with changes in p-mTOR, Bcl-2, Bax, and cleaved caspase-3 expression, as well as the number of apoptotic cells. In vitro, H9C2 cardiomyocyte viability was significantly inhibited and cardiac hypertrophy was induced by Ang II administration, but ALS reversed Ang II-induced H9C2 cardiomyocyte hypertrophy and death. Furthermore, Ang II triggered the activation of the mTOR and apoptosis pathways in hypertrophic cardiomyocytes that were inhibited by ALS treatment. These results indicated that ALS alleviated cardiac hypertrophy through inhibition of the mTOR and apoptosis pathways in cardiomyocytes.


Subject(s)
Animals , Male , Rats , Apoptosis/drug effects , Cardiomegaly/prevention & control , TOR Serine-Threonine Kinases/metabolism , Fumarates/administration & dosage , Amides/administration & dosage , Fibrosis/chemically induced , Fibrosis/prevention & control , Angiotensin II/pharmacology , Signal Transduction/drug effects , Blotting, Western , Rats, Sprague-Dawley , Cardiomegaly/chemically induced , Cardiomegaly/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Disease Models, Animal , TOR Serine-Threonine Kinases/drug effects , Flow Cytometry , Isoproterenol/pharmacology
3.
Article in Chinese | WPRIM | ID: wpr-775058

ABSTRACT

OBJECTIVE@#To study the changes and significance of apoptosis signal-regulating kinase 1 (ASK1) in left ventricular remodeling in FVB/N mice.@*METHODS@#A total of 54 FVB/N mice were randomly divided into 4 groups: 0 d group with 8 mice, 7 d group with 10 mice, 14 d group with 16 mice, and 21 d group with 20 mice. A model of cardiac remodeling was established by intraperitoneal injection of isoproterenol (ISO) at a daily dose of 30 mg/kg, and the 7 d, 14 d, and 21 d groups were injected for 7, 14, and 21 consecutive days respectively. The 0 d group was given intraperitoneal injection of an equal volume of normal saline. Echocardiography was used to measure left ventricular posterior wall thickness at end diastole (dLVPW) and the ratio of heart weight to tibia length (HW/TL) was measured. Hematoxylin-eosin staining was used to measure left ventricular myocardial fiber diameter. Picric-Sirius red staining was used to measure myocardial collagen deposition area in the left ventricle. Quantitative real-time PCR was used to measure the mRNA expression of ASK1, type I collagen (collagen I), and B-type natriuretic peptide (BNP). The mortality rate was observed for each group.@*RESULTS@#There were gradual increases in HW/TL, myocardial fiber diameter, and dLVPW after 0, 7, and 14 days of ISO injection (P0.05), while there was a significant reduction in myocardial fiber diameter (P0.05). There were significant increases in myocardial collagen deposition area and the mRNA expression of collagen I, ASK1, and BNP after 0, 7, 14, and 21 days of ISO injection, which reached the peaks on day 21 (P<0.01). The mRNA expression of ASK1 was positively correlated with myocardial collagen deposition area and the mRNA expression of collagen I and BNP and had a weak correlation with HW/TL, myocardial fiber diameter, and dLVPW. There was a significant increase in the mortality rate of the mice over the time of ISO injection.@*CONCLUSIONS@#The expression of ASK1 in the myocardium is closely associated with left ventricular remodeling. The increase of ASK1 expression may lead to the aggravation of left ventricular remodeling, and the mechanism of which needs further study.


Subject(s)
Animals , Isoproterenol , MAP Kinase Kinase Kinase 5 , Mice , Myocardium , Myocytes, Cardiac , Ventricular Remodeling
4.
Article in English | WPRIM | ID: wpr-761783

ABSTRACT

The present study was designed to examine the effect of heme oxygenase-1 (HO-1) induction by cobalt protoporphyrin (CoPP) on the cardiac functions and morphology, electrocardiogram (ECG) changes, myocardial antioxidants (superoxide dismutase [SOD] and glutathione [GSH]), and expression of heat shock protein (Hsp) 70 and connexin 43 (Cx-43) in myocardial muscles in isoproterenol (ISO) induced myocardial infarction (MI). Thirty two adult male Sprague Dawely rats were divided into 4 groups (each 8 rats): normal control (NC) group, ISO group: received ISO at dose of 150 mg/kg body weight intraperitoneally (i.p.) for 2 successive days; ISO + Trizma group: received (ISO) and Trizma (solvent of CoPP) at dose of 5 mg/kg i.p. injection 2 days before injection of ISO, with ISO at day 0 and at day 2 after ISO injections; and ISO + CoPP group: received ISO and CoPP at a dose of 5 mg/kg dissolved in Trizma i.p. injection as Trizma. We found that, administration of ISO caused significant increase in heart rate, corrected QT interval, ST segment, cardiac enzymes (lactate dehydrogenase, creatine kinase-muscle/brain), cardiac HO-1, Hsp70 with significant attenuation in myocardial GSH, SOD, and Cx-43. On the other hand, administration of CoPP caused significant improvement in ECG parameters, cardiac enzymes, cardiac morphology; antioxidants induced by ISO with significant increase in HO-1, Cx-43, and Hsp70 expression in myocardium. In conclusions, we concluded that induction of HO-1 by CoPP ameliorates ISO-induced myocardial injury, which might be due to up-regulation of Hsp70 and gap junction protein (Cx-43).


Subject(s)
Adult , Animals , Antioxidants , Body Weight , Cobalt , Connexin 43 , Connexins , Creatine , Electrocardiography , Glutathione , Hand , Heart Rate , Heat-Shock Proteins , Heme Oxygenase-1 , Heme , HSP70 Heat-Shock Proteins , Humans , Isoproterenol , Male , Muscles , Myocardial Infarction , Myocardium , Oxidoreductases , Rats , Tromethamine , Up-Regulation
5.
Acta cir. bras ; 34(5): e201900505, 2019. graf
Article in English | LILACS | ID: biblio-1010872

ABSTRACT

Abstract Purpose: To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. Methods: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. Results: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of β-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of β-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). Conclusion: The pharmacological modulation of β-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.


Subject(s)
Animals , Male , Atenolol/pharmacology , Cardiotonic Agents/pharmacology , Myocardial Reperfusion Injury/drug therapy , Receptors, Adrenergic, beta/drug effects , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-1 Receptor Antagonists/pharmacology , Isoproterenol/pharmacology , Rats, Inbred SHR , Time Factors , Blood Pressure/drug effects , Biomarkers/blood , Myocardial Reperfusion Injury/physiopathology , Myocardial Reperfusion Injury/blood , Reproducibility of Results , Treatment Outcome , Creatine Kinase, MB Form/blood , Heart Function Tests
6.
Arq. bras. cardiol ; 111(3): 400-409, Sept. 2018. tab, graf
Article in English | LILACS | ID: biblio-973754

ABSTRACT

Abstract Background: Caloric restriction is known to impair the cardiac function and morphology in hypertrophied hearts of spontaneously hypertensive rats (SHR); however, the influence of fasting/refeeding (RF) is unknown. Objective: To investigate the fasting/refeeding approach on myocardial remodeling and function. In addition, the current study was designed to bring information regarding the mechanisms underlying the participation of Ca2+ handling and b-adrenergic system. Methods: Sixty-day-old male SHR rats were submitted to food ad libitum (C), 50% food restriction (R50) or RF cycles for 90 days. Cardiac remodeling was assessed by ultrastructure analysis and isolated papillary muscle function. The level of significance considered was 5% (a = 0.05). Results: The RF rats presented lower cardiac atrophy than R50 in relation to C rats. The C rats increased weight gain, R50 maintained their initial body weight and RF rats increased and decreased weight during RF. The RF did not cause functional impairment because the isotonic and isometric parameters showed similar behavior to those of C. The isotonic and isometric cardiac parameters were significantly elevated in RF rats compared to R50 rats. In addition, the R50 rats had cardiac damage in relation to C for isotonic and isometric variables. While the R50 rats showed focal changes in many muscle fibers, the RF rats displayed mild alterations, such as loss or disorganization of myofibrils. Conclusion: Fasting/refeeding promotes cardiac beneficial effects and attenuates myocardial injury caused by caloric restriction in SHR rats, contributing to reduce the cardiovascular risk profile and morphological injuries. Furthermore, RF promotes mild improvement in Ca2+ handling and b-adrenergic system.


Resumo Fundamento: A restrição calórica compromete a função e a morfologia cardíacas em corações hipertrofiados de ratos espontaneamente hipertensos (SHR). No entanto, a influência de ciclo de jejum/Realimentação é desconhecida. Objetivo: Investigar o efeito de ciclos de jejum/realimentação sobre a remodelação e função miocárdica. Além disso, o presente estudo foi desenhado para avaliar os mecanismos subjacentes à participação do trânsito de cálcio (Ca+2) e sistema beta-adrenérgico. Métodos: Neste estudo, SHR machos de 60 dias de idade foram submetidos a alimento ad libitum (grupo C), 50% de restrição alimentar (grupo R50) ou ciclos de RF (grupo RF) por 90 dias. A remodelação cardíaca foi avaliada por meio da análise ultraestrutural e função do músculo papilar isolado. Adotou-se o nível de significância de 5% (a = 0,05). Resultados: Os ratos do grupo RF apresentaram menor atrofia cardíaca do que os do grupo R50 em relação aos do grupo C. Os ratos do grupo C aumentaram peso corporal, os ratos do grupo R50 mantiveram seu peso corporal inicial e os ratos do grupo RF aumentaram e reduziram seu peso durante o ciclo RF. O ciclo RF não causou comprometimento funcional, pois os parâmetros isotônicos e isométricos apresentaram comportamento similar aos dos ratos do grupo C. Os parâmetros cardíacos isotônicos e isométricos mostraram-se significativamente elevados nos ratos do grupo RF em comparação aos dos ratos do grupo R50. Além disso, os ratos do grupo R50 apresentaram dano cardíaco em comparação aos ratos do grupo C quanto às variáveis isotônicas e isométricas. Os ratos do grupo R50 apresentaram alterações focais em muitas fibras musculares, enquanto os ratos do grupo RF apresentaram leves alterações, como perda ou desorganização de miofibrilas. Conclusão: Ciclos de Jejum/Realimentação promovem efeitos benéficos cardíacos e atenuam o dano miocárdico causado por restrição calórica em SHR, contribuindo para reduzir o risco cardiovascular e os danos morfológicos. Além disso, o ciclo de jejum/realimentação promove leve melhora do trânsito do Ca2+ e do sistema beta-adrenérgico.


Subject(s)
Animals , Male , Papillary Muscles/metabolism , Calcium/metabolism , Fasting/physiology , Animal Nutritional Physiological Phenomena/physiology , Cardiomyopathies/prevention & control , Papillary Muscles/pathology , Rats, Inbred SHR , Time Factors , Body Weight/physiology , Calcium/analysis , Ventricular Remodeling/physiology , Caloric Restriction/adverse effects , Isoproterenol/analysis , Isoproterenol/metabolism , Myocardial Contraction , Cardiomyopathies/pathology
8.
Article in Chinese | WPRIM | ID: wpr-771665

ABSTRACT

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 , Cardiomegaly , Drug Therapy , Dendrobium , Chemistry , Drugs, Chinese Herbal , Pharmacology , Female , Isoproterenol , Male , Myocardium , Pathology , Rats , Rats, Sprague-Dawley
9.
Article in Chinese | WPRIM | ID: wpr-689598

ABSTRACT

<p><b>OBJECTIVE</b>To explore the feasibility of intraperitoneal injection of isoproterenol (ISO) to induce cardiac remodeling in FVB/N mice.</p><p><b>METHODS</b>Forty-eight FVB/N mice were divided into back subcutaneous saline group (subcutaneous saline group), intraperitoneal saline group, back subcutaneous ISO group (subcutaneous ISO group), and intraperitoneal ISO group according to the route of administration of saline or ISO. ISO (30 μg/g body weight/day) was given to the subcutaneous ISO group and the intraperitoneal ISO group, twice daily with an interval of 12 hours, for 14 consecutive days. The subcutaneous saline group and the intraperitoneal saline group were injected with an equal volume of saline. The left ventricular end-diastolic posterior wall thickness was measured by echocardiography, and the ratio of heart weight to tibia length was determined. Hematoxylin-eosin staining was used to determine the myocardial fiber diameter. Picric-sirius red staining was used to determine the myocardial collagen deposition area. Quantitative real-time PCR was used to measure the mRNA expression of collagen I.</p><p><b>RESULTS</b>Compared with the subcutaneous ISO, subcutaneous saline, and intraperitoneal saline groups, the intraperitoneal ISO group had increased sizes of the cardiac cavity and the heart. Compared with the subcutaneous saline and intraperitoneal saline groups, the subcutaneous ISO group showed no significant changes in the gross morphology of the cardiac cavity and the heart. The intraperitoneal ISO group showed significant increases in the ratio of heart weight to tibia length, myocardial fiber diameter, left ventricular end-diastolic posterior wall thickness, myocardial collagen area percentage, and the mRNA expression of collagen I compared with the subcutaneous ISO, subcutaneous saline, and intraperitoneal saline groups (P<0.01). There were no significant differences in the above five indices between the subcutaneous ISO group and the subcutaneous saline and intraperitoneal saline groups (P>0.05). No significant difference in the mortality rate was found between the subcutaneous ISO and intraperitoneal ISO groups (P>0.05).</p><p><b>CONCLUSIONS</b>Intraperitoneal injection of ISO can induce cardiac hypertrophy and fibrosis in FVB/N mice.</p>


Subject(s)
Animals , Atrial Remodeling , Cardiovascular Diseases , Drug Therapy , Metabolism , Pathology , Collagen , Metabolism , Disease Models, Animal , Humans , Injections, Intraperitoneal , Isoproterenol , Male , Mice , Myocardium , Metabolism , Pathology
10.
Article in English | WPRIM | ID: wpr-740061

ABSTRACT

Increased intracellular levels of Ca²⁺ are generally thought to negatively regulate lipolysis in mature adipocytes, whereas store-operated Ca²⁺ entry was recently reported to facilitate lipolysis and attenuate lipotoxicity by inducing lipophagy. Transient receptor potential mucolipin1 (TRPML1), a Ca²⁺-permeable non-selective cation channel, is mainly expressed on the lysosomal membrane and plays key roles in lysosomal homeostasis and membrane trafficking. However, the roles of TRPML1 in lipolysis remains unclear. In this study, we examined whether the channel function of TRPML1 induces lipolysis in mature adipocytes. We found that treatment of mature adipocytes with ML-SA1, a specific agonist of TRPML1, solely upregulated extracellular glycerol release, but not to the same extent as isoproterenol. In addition, knockdown of TRPML1 in mature adipocytes significantly reduced autophagic flux, regardless of ML-SA1 treatment. Our findings demonstrate that the channel function of TRPML1 partially contributes to lipid metabolism and autophagic membrane trafficking, suggesting that TRPML1, particularly the channel function of TRPML1, is as therapeutic target molecule for treating obesity.


Subject(s)
Adipocytes , Glycerol , Homeostasis , Isoproterenol , Lipid Metabolism , Lipolysis , Membranes , Obesity
11.
Rev. colomb. anestesiol ; 46(4): 341-344, 2018.
Article in English | LILACS, COLNAL | ID: biblio-978218

ABSTRACT

Abstract A case of intraoperative awareness during ablation of pulmonary veins-one of the most widely used techniques in interventional cardiology-is discussed. An infusion of isoproterenol was administered following the ablation of ectopic foci. A few seconds after the infusion the patient experienced increased heart rate and intraoperative awareness manifested as an abrupt patient movement and bispectral index elevation. This has been described in similar procedures, following the administration of isoproterenol. In our opinion, the isoproterenol infusion caused the increased heart rate and subsequent abrupt rise in cardiac output. As an inversely proportional relationship between the propofol concentrations and cardiac output has been described, we believe that this rise in cardiac output could have favored the decline in the concentrations of propofol, leading to an intraoperative awareness episode.


Resumen Presentamos un caso de despertar intraoperatorio durante la ablación de venas pulmonares, una de las técnicas más empleadas por los cardiólogos intervencionistas. Tras la ablación de focos ectópicos se procede a la infusión de isoproterenol. Segundos después de la infusión se produce un aumento de la frecuencia cardíaca seguido de un despertar intraoperatorio traducido como un movimiento brusco del paciente y un aumento en el índice bi-espectral (BIS). Esto ha sido descrito en procedimientos similares tras la administración de isoproterenol. En nuestra opinión, la infusión de isoproterenol provocó un aumento de la frecuencia cardiaca y secundariamente del gasto cardíaco de forma brusca. Dado que se ha descrito una relación inversamente propocional entre las concentraciones de propofol y el gasto cardíaco, pensamos que este aumento del gasto cardíaco pudo condicionar un descenso de las concentraciones de propofol y esto causar el episodio de despertar intraoperatorio.


Subject(s)
Humans , Middle Aged , Pulmonary Veins , Cardiac Output , Propofol , Catheter Ablation , Intraoperative Awareness , Isoproterenol , Anesthetics , Cardiology , Ruscus , Cardiologists , Heart Rate
12.
Cell Journal [Yakhteh]. 2017; 19 (1): 84-93
in English | IMEMR | ID: emr-185795

ABSTRACT

Objective: Lavender is used in herbal medicine for different therapeutic purposes. Nonetheless, potential therapeutic effects of this plant in ischemic heart disease and its possible mechanisms remain to be investigated


Materials and Methods: In this experimental study, lavender oil at doses of 200, 400 or 800 mg/kg was administered through gastric gavage for 14 days before infarct-like myocardial injury [MI]. The carotid artery and left ventricle were cannulated to record arterial blood pressure [BP] and cardiac function. At the end of experiment, the heart was removed and histopathological alteration, oxidative stress biomarkers as well as tumor necrosis factor-alpha [TNF-alpha] level were evaluated


Results: Induction of M.I caused cardiac dysfunction, increased levels of lipid peroxidation, TNF-alpha and troponin I in heart tissue [P<0.001]. Pretreatment with lavender oil at doses of 200 and 400 mg/kg significantly reduced myocardial injury, troponin I and TNF-alpha. In addition, it improved cardiac function and antioxidant enzyme activity [P<0.01]


Conclusion: Our finding showed that lavender oil has cardioprotective effect through inhibiting oxidative stress and inflammatory pathway in the rat model with infarct-like MI. We suggest that lavender oil may be helpful in prevention or attenuation of heart injury in patients with high risk of myocardial infarction and/or ischemic heart disease


Subject(s)
Animals, Laboratory , Male , Myocardial Infarction , Tumor Necrosis Factor-alpha/drug effects , Disease Models, Animal , Rats, Wistar , Isoproterenol , Oxidative Stress
13.
Article in Korean | WPRIM | ID: wpr-71032

ABSTRACT

PURPOSE: A combination of β1-adrenergic receptor (β₁-AR) blockade and β₂-AR activation might potentially be the novel therapy for treating heart failure. However, the use of β-AR agonists and/or antagonists in the clinical setting is controversial due to the lack of information on cardiac inotropic or chronotropic regulation by AR signaling. METHODS: In this study, we performed a hemodynamic evaluation by examining the force frequency response (FFR), Frank-Starling relationship, and response to non-selective β-AR agonist (isoproterenol) in the hearts isolated from 6-month-old transgenic (TG) mice overexpressing β₁- and β₂-ARs (β₁- and β₂-AR TG mice, respectively). RESULTS: Cardiac physiologic consequences of β₁- and β₂-AR overexpression resulted in a similar maximal response to that of isoproterenol and faster temporary decline of positive inotropic response in β₂-AR TG mice. β₁-AR TG mice showed a pronounced negative limb of FFR, whereas β2-AR TG mice showed high stimulation frequencies with low contractile depression during FFR. Contrastingly, Frank-Starling relationship was equally enhanced in both β₁- and β₂-AR TG mice. CONCLUSION: Hemodynamic evaluation performed in the present study showed a difference between β₁- and β₂-AR signaling, which may be due to a difference in the desensitization of β₁- and β₂-ARs.


Subject(s)
Animals , Depression , Extremities , Heart , Heart Failure , Hemodynamics , Humans , Infant , Isoproterenol , Mice , Mice, Transgenic , Receptors, Adrenergic
14.
Article in English | WPRIM | ID: wpr-29541

ABSTRACT

BACKGROUND: Whartons jelly-derived mesenchymal stem cells are a valuable alternative source that possess multipotent properties, easy to obtain and available in large scale compared to BMMSCs. We investigated the possibility of cardiac function improvement post isoproterenol induced cardiac injury in a rat model following human WJMSCs transplantation. MATERIALS AND METHODS: MSCs were extracted and cultured from cord WJ, characterized by morphology, Immunophenotyping and differentiation to osteoblast and adipocytes. WJMSCs were labeled with PKH2 linker dye. Wistar rats were divided into control group, ISO group (injected with 2 doses of isoproterenol) to induce myocardial injury and ISO group transplanted with labelled WJMSCs. ECG, electrocardiographic patterns, cardiac marker enzymes, tracing of labeled MSCs and immunohistochemical analysis of myocardial cryosections were studied. RESULTS AND CONCLUSIONS: WJ derived MSCs were expanded for more than 14 passages while maintaining their un-differentiated state, were positive for MSC markers and were able to differentiate into adipocyte and osteoblast. We demonstrated that intravenously administered WJMSCs were capable of homing predominently in the ischemic myocardium. Cardiac markers were positively altered in stem cell treated group compared to ISO group. ECG and ECHO changes were improved with higher survival rate. WJMSCs could differentiate into cardiac-like cells (positive for cardiac specific proteins) in vivo. WJMSCs infusion promoted cardiac protection and reduced mortality, emphasizing a promising therapeutic role for myocardial insufficiency.


Subject(s)
Adipocytes , Electrocardiography , Humans , Immunophenotyping , Isoproterenol , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Models, Animal , Mortality , Myocardium , Osteoblasts , Rats, Wistar , Rodentia , Stem Cells , Survival Rate , Transplantation , Wharton Jelly
15.
Article in English | WPRIM | ID: wpr-30374

ABSTRACT

This study was performed to investigate the signaling pathway that mediates cyclic AMP (cAMP)-induced inhibition of histone deacetylase 8 (HDAC8) degradation, and the effect and underlying mechanisms of the resulting increase in HDAC8 expression on cisplatin-induced apoptosis in lung cancer cells. cAMP signaling increased HDAC8 expression via a protein kinase A (PKA)-independent pathway in H1299 non-small cell lung cancer cells. However, treatment with a selective activator of an exchange protein that was activated by cAMP (Epac) increased HDAC8 expression, and Epac2 inhibition abolished the isoproterenol (ISO)-induced increase in HDAC8 expression. ISO and the Epac activator activated Rap1, and Rap1A activation increased HDAC8 expression; moreover, inhibition of Rap1A with a dominant negative Rap1A or by shRNA-mediated knockdown abolished the ISO-induced increase in HDAC8 expression. Activation of cAMP signaling and Rap1A decreased the activating phosphorylation of Akt. Akt inhibition with a pharmacological inhibitor or expression of a dominant negative Akt inhibited the MKK4/JNK pathway and increased HDAC8 expression. The Akt inhibitor-induced increase in HDAC8 expression was abolished by pretreatment with proteasomal or lysosomal inhibitors. The ISO treatment increased cisplatin-induced apoptosis, which was abolished by HDAC8 knockdown. Exogenous HDAC8 expression increased cisplatin-induced apoptosis and decreased TIPRL expression, and the knockdown of TIPRL increased the apoptosis of cisplatin-treated cells. The ISO treatment decreased cisplatin-induced transcription of the TIPRL gene in a HDAC8-dependent manner. In conclusion, the Epac–Rap1–Akt pathway mediates cAMP signaling-induced inhibition of JNK-dependent HDAC8 degradation, and the resulting HDAC8 increase augments cisplatin-induced apoptosis by repressing TIPRL expression in H1299 lung cancer cells.


Subject(s)
Apoptosis , Carcinoma, Non-Small-Cell Lung , Cyclic AMP , Cyclic AMP-Dependent Protein Kinases , Histone Deacetylases , Histones , Isoproterenol , Lung Neoplasms , Lung , Phosphorylation
16.
Int. j. cardiovasc. sci. (Impr.) ; 29(1): 19-23, jan.-fev.2016. ilus
Article in Portuguese | LILACS | ID: lil-797108

ABSTRACT

O infarto agudo do miocárdio (IAM) é uma situação clínica determinada por processo isquêmicoagudo, que resulta em necrose miocárdica. Os marcadores cardíacos em caso de isquemia reversível, atualmente,apresentam sensibilidade limitada.Objetivo: Verificar a sensibilidade da albumina modificada isquêmica (AMI), como marcador cardíaco. Métodos: Estudo experimental, realizado no Laboratório de Experimentação Animal da Universidade Regional Integrada (URI), Erechim, RS, no período de 2011 a 2013. Após a indução isquêmica do miocárdio em ratos da linhagem Wistar-Tecpar, com idade aproximada entre 60-90 dias, através da administração de isoproterenol hidrocloridrato, o conteúdo da AMI foi avaliado em diferentes tempos. Resultados: Os valores da AMI mantiveram-se diminuídos durante as três horas iniciais, após a indução isquêmica pelo isoproterenol hidrocloridrato. Conclusão: Neste estudo, a albumina modificada pela isquemia foi considerada um marcador sensível,principalmente nas três horas iniciais da isquemia...


Background: Acute myocardial infarction (AMI) is a condition determined by an acute ischemic process resulting in myocardial necrosis. Cardiac markers in reversible ischemia currently have limited sensitivity. Objective: To check the sensitivity of ischemia modified albumin (IMA) as a cardiac marker.Methods: Experimental study held at the Animal Experimentation Laboratory of Universidade Regional Integrada (URI), Erechim, RS, from 2011 to 2013. After myocardial ischemic induction in Wistar-Tecpar rats aged about 60-90 days through administration of isoproterenol hydrochloride, the IMA content was evaluated at different times. Results: The IMA values remained reduced during the three first hours after ischemic induction by isoproterenol hydrochloride.Conclusion: In this study, ischemia modified albumin was considered a sensitive marker, particularly in the first three hours of ischemia...


Subject(s)
Animals , Rats , Albumins , Myocardial Ischemia/complications , Myocardial Ischemia/physiopathology , Rats, Wistar , Sensitivity and Specificity , Analysis of Variance , Animal Experimentation , Cardiovascular Diseases/mortality , Myocardial Infarction/epidemiology , Myocardial Infarction/physiopathology , Isoproterenol/administration & dosage , Treatment Outcome , Histological Techniques/methods , Troponin I/administration & dosage
17.
IJPR-Iranian Journal of Pharmaceutical Research. 2016; 15 (1): 107-117
in English | IMEMR | ID: emr-177541

ABSTRACT

The electrocatalytic oxidation of captopril [CAP] was studied by modified carbon nanotubes paste electrode in the presence of isoproterenol [ISPT] using cyclic voltammetry [CV], chronoamperometry and square wave voltammetry [SWV]. Also, the values of catalytic rate constant [k], and electron transfer coefficient [alpha] for CAP were calculated. The mechanism of CA electrochemical behavior at the modified electrode surface was analyzed by various electrochemical methods in the presence of mediator. The prepared modified electrode showed voltammetric responses with high sensitivity for CAP, making it very suitable for the detection of CAP at trace levels. Under the optimized conditions, the peak current was linear to CAP concentration over the concentration range of 0.3 to 90 micromol L[-1] using SWV. The detection limit was 0.1 micromol L[-1]. The proposed method was successfully applied to the determination of CAP in the urine, tablet and patient urine samples


Subject(s)
Nanotubes, Carbon , Alcohols , Drug Combinations , Isoproterenol
18.
Article in English | WPRIM | ID: wpr-644693

ABSTRACT

OBJECTIVE: Combination of β₁-adrenergic receptor (AR) blockade and β₂-AR activation might be a potential novel therapy for treating heart failure. However, use of β-AR agonists and/or antagonists in the clinical setting is controversial because of the lack of information on cardiac inotropic or chronotropic regulation by AR signaling. METHODS: In this study, we performed hemodynamic evaluation by examining force frequency response (FFR), Frank-Starling relationship, and response to a non-selective β-AR agonist (isoproterenol) in hearts isolated from 6-month-old transgenic (TG) mice overexpressing β₁- and β₂-ARs (β₁- and β₂-AR TG mice, respectively). RESULTS: Cardiac physiologic consequences of β₁- and β₂-AR overexpression resulted in similar maximal response to isoproterenol and faster temporary decline of positive inotropic response in β₂-AR TG mice. β₁-AR TG mice showed a pronounced negative limb of FFR, whereas β₂-AR TG mice showed high stimulation frequencies with low contractile depression during FFR. In contrast, Frank-Starling relationship was equally enhanced in both β₁- and β₂-AR TG mice. CONCLUSION: Hemodynamic evaluation performed in the present showed a difference in β₁- and β₂-AR signaling, which may be due to the difference in the desensitization of β₁- and β₂-ARs.


Subject(s)
Animals , Depression , Extremities , Heart , Heart Failure , Hemodynamics , Humans , Infant , Isoproterenol , Mice , Mice, Transgenic , Receptors, Adrenergic
19.
Chinese Medical Journal ; (24): 2676-2682, 2016.
Article in English | WPRIM | ID: wpr-230901

ABSTRACT

<p><b>BACKGROUND</b>β-adrenoceptors play a crucial regulatory role in blood vessel endothelial cells. Isoprenaline (ISO, a β-adrenergic agonist) has been reported to promote angiogenesis through upregulation of vascular endothelial growth factor (VEGF) expression; however, the underlying mechanism remains to be investigated. It is widely accepted that certain noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), can regulate endothelial cell behavior, including their involvement in angiogenesis. Therefore, we aimed to investigate whether noncoding RNAs participate in ISO-mediated angiogenesis using human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>We evaluated VEGF-A messenger RNA (mRNA) and protein levels in ISO-treated HUVECs by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. To establish whether noncoding RNAs are associated with ISO-mediated angiogenesis, we measured expression of the miRNAs miR-210, miR-21, and miR-1, as well as that of the lncRNAs growth arrest-specific transcript 5 (GAS5), maternally expressed 3 (MEG3), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HUVECs exposed to ISO. Furthermore, to ascertain its importance in ISO-mediated angiogenesis, we constructed the HUVECs with overexpressing miR-210 and detected the subsequent expression of VEGF-A and noncoding RNAs. All statistical analyses were performed using SPSS 16.0 software. Intergroup comparisons were carried out by one-way analysis of variance.</p><p><b>RESULTS</b>VEGF-A mRNA levels were elevated in the ISO group (1.57 ± 0.09) compared to those in the control group (P < 0.01). Moreover, concentrations of VEGF-A in culture supernatants significantly differed between the control (113.00 ± 19.21 pg/ml) and ISO groups (287.00 ± 20.27 pg/ml; P< 0.01). Expression of miR-1, miR-21, and miR-210 was higher (3.89 ± 0.44, 2.87 ± 087, and 3.33 ± 1.31, respectively) in ISO-treated cells than that in controls (P < 0.01), whereas that of GAS5 and MEG3 (0.22 ± 0.10 and 0.58 ± 0.16, respectively) was lower as a result of ISO administration (P < 0.05). There was no significant difference in the expression of MALAT1 between the groups. Interestingly, miR-210 overexpression heightened the levels of VEGF-A and miR-21 (5.87 ± 1.24 and 2.74 ± 1.15, respectively; P< 0.01) and reduced those of GAS5 and MEG3 (0.19 ± 0.01 and 0.09 ± 0.05, respectively; P< 0.01).</p><p><b>CONCLUSIONS</b>ISO-mediated angiogenesis was associated with altered expression of miR-210, miR-21, and the lncRNAs GAS5 and MEG3. The effects of miR-210 on the expression of VEGF-A and noncoding RNAs were similar to those of ISO, indicating that it might play an important role in ISO-mediated angiogenesis.</p>


Subject(s)
Cell Line , Cell Survival , Human Umbilical Vein Endothelial Cells , Metabolism , Humans , Isoproterenol , Pharmacology , MicroRNAs , Genetics , Physiology , Neovascularization, Pathologic , Genetics , RNA, Long Noncoding , Genetics , Real-Time Polymerase Chain Reaction , Vascular Endothelial Growth Factor A , Metabolism
20.
Article in Chinese | WPRIM | ID: wpr-286310

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effect of Kanli Granule (KG) on myocardial mechanics in pressure overload induced diastolic heart failure (DHF) rats.</p><p><b>METHODS</b>Totally 60 male Wistar rats were divided into the sham-operation group, the model group, the KG group, and the Valsartan group according to random digit table, 15 in each group. The pressure overload induced DHF model was established in all groups except the sham-operation group using abdominal aortic constriction surgery. Totally 7 rats died after modeling (with the mortality of 10. 67%) , and the rest 53 finished the following test. Rats in the KG group were administered with KG extract (calculated as 6. 75 g crude drug/kg) by gastrogavage. Rats in the Valsartan group were administered with Valsartan (7.2 µg/g) by gastrogavage. Equal volume of double distilled water was administered to rats in the model group and the sham-operation group by gastrogavage. All rats were intervened for 32 weeks. The response of isolated heart papillary muscle tonus to isoprenaline (ISO) and adenylate cyclase (Forskolin) was respectively observed. The enhancement phenomenon after resting development force (DF) of isolated heart papillary muscle tonus, and changes of DF in different Ca²⁺ concentrations were observed.</p><p><b>RESULTS</b>(1) In the ISO response test: Compared with the sham-operation group, the amplifications of DF, ±df/dt, -df/dt were obviously elevated in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously lowered in the KG group (P < 0.01), and the amplification of ±df/dt was also reduced in the Valsartan group (P < 0.01). (2) In the Forskolin response test: Compared with the sham-operation group, the amplifications of DF and ±df/dt obviously increased in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously reduced in the KG group (P < 0.01), and the amplification of DF was also reduced in the Valsartan group (P < 0.05). (3) In post-resting DF enhancement test: Compared with the sham-operation group, the amplification of DF showed gradually decreasing tendency along with prolonged resting time in the model group, and they were obviously lowered at all time points (P < 0.05). Compared with the model group, the amplification of DF was gradually increasing along with prolonged resting time in the KG group. The amplification of DF at post-resting 240 s was obviously larger in the KG group than in the model group (P < 0.05). The amplification of post-resting DF still showed gradually decreasing tendency along with prolonged resting time in the Valsartan group, with increased amplifications of DF at post-resting 60 s and 120 s (P < 0. 05) (4) The amplifications of DF in different Ca²⁺ concentrations: Compared with the sham-operation group, the amplifications of DF were significantly elevated in different Ca²⁺ concentrations (1.75, 3.5, 7.0 mmol/L ) (P < 0.05, P < 0.01). Compared with the model group, there was no statistical difference in amplification of DF in different Ca²⁺ concentrations in the KG group (P > 0.05). The amplifications of DF in different Ca²⁺ concentrations were significantly reduced in the Valsartan group (P < 0.05).</p><p><b>CONCLUSIONS</b>The ISO response and the Forskolin response were enhanced in isolated heart papillary muscle tonus of pressure overload induced DHF rats; enhanced post-resting DF was reduced; DF in different supra-physiologic levels of Ca²⁺ was still enhanced. KG could significantly improve excessive enhancement of pressure overload induced DHF rats in ISO response and Forskolin response, and improve enhancement of post-resting myocardium.</p>


Subject(s)
Animals , Colforsin , Pharmacology , Drugs, Chinese Herbal , Pharmacology , Heart , Heart Failure, Diastolic , Drug Therapy , Isoproterenol , Pharmacology , Male , Random Allocation , Rats , Rats, Wistar
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