Expression of p-PPARγ in the aging thoracic aorta of spontaneously hypertensive rat and inhibitory effect of rosiglitazone

Objective: To investigate the expression of phosphorylated peroxisome proliferators-activated receptor γ (p-PPARγ) in the aging thoracic aorta of spontaneously hypertensive rat (SHR) and the inhibitory effect of rosiglitazone on the phosphorylation of PPARγ. Methods: 16, 32 and 64 week-old Wistar-Kyoto rats (WKY) and SHR were randomly and respectively divided into WKY, SHR and SHR+rosiglitazone group (9 in each group). The rats in SHR+rosiglitazone group were treated with rosiglitazone (5 mg/kg, intragastrically) for 56 d, whereas normal saline was applied in WKY and SHR groups. Systolic blood pressure (SBP) of rats was measured by tail cuff method. Histopathological damage of thoracic aorta was analyzed using Hematoxylin-Eosin (HE) staining. Immunohistochemical staining and western blot were performed to test the level of p-PPARγ protein in the thoracic aorta arising from each group. Results: The SBP in 16, 32 and 64 week-old SHR were significantly higher as compared with those in matched WKY rats (P < 0.05, respectively). HE staining showed increased content of smooth muscle cell, wrinkled lining endothelium and increased thickness of internal elastic lamina in the thoracic aorta of SHR. Immunohistochemical staining and western blot indicated that the levels of p-PPARγ in the thoracic aorta arising from SHR were obviously higher than those in the thoracic aorta arising from WKY rats (P < 0.05, respectively). Importantly, the high SBP, histopathological abnormalities of the thoracic aorta and elevated p-PPARγ expression were prominently abrogated by rosiglitazone treatment in SHR (P < 0.05, respectively). Furthermore, the SBP, histopathological abnormalities of the thoracic aorta and p-PPARγ expression were positively correlated with age in SHR (P < 0.05, respectively). Conclusions: The PPARγ phosphorylation was observed in the thoracic aorta of SHR and its expression was increased by the increase of age. Furthermore, rosiglitazone inhibited the PPARγ phosphorylation and suppressed vascular aging in SHR.

Preliminary implementation and effect of clinical pathways for chronic Keshan disease in endemic areas / 中国地方病学杂志

Objective This present study explores and evaluates the effect of preliminary implementation in the clinical therapy programs for patients with chronic Keshan disease (CKD) in the disease seriously-affected endemic areas.Methods In 2010,seventy-six CKD patients with heart failure were chosen from Huangling and Xunyi Counties in Shaanxi Province,where incidences of CKD were high.Besides taking sodium selenite,all patients were given treatment with fixed prescription,which included angiotensin-converting enzyme inhibitor (captopril),β-blocker (propranolol),diuretics (hydrochlorothiazide,spironolactone) and cardiac (digoxin) for 4 months.The changes before and after treatment were analyzed,which included the changes of heart function by the United States of America New York Heart Association(NYHA) fractionation,cardiothoracic ratio,electrocardiogram,left ventricular ejection fraction(EF) and fractional shortening(FS).The therapeutic effect was subsequently evaluated.Results Seventy-four cases of the seventy-six CKD patients completed the treatment observation.The improvement rate of heart function was 81.1％ (60/74) after treatment.The elimination rates of ectopic rhythm,conduction block and ST-T changes were 37.5％ (9/24),2.7％ (1/36) and 26.9％ (7/26),respectively.The cardiothoracic ratios of heart function NYHA Ⅱ,Ⅲ and Ⅳ were 0.504 ± 0.051,0.572 ± 0.054 and 0.632 ± 0.063 before treatment.After treatment,the cardiothoracic ratios were 0.486 ± 0.048,0.538 ± 0.046 and 0.607 ± 0.048,which were reduced in all groups (t =2.643,6.641,3.005,all P ＜ 0.05),while the D-value of cardiothoracic ratio changes before and after treatment was not significantly different(F =3.005,P ＞ 0.05).Both the mild reduction group(35％≤EF ＜ 50％) and the moderate-severe group(EF ＜ 35％) EF were (43.62 ± 4.58)％,(27.57 ± 3.69)％ before treatment and were (48.21 ± 10.01)％,(36.57 ± 6.60)％ after treatment,EF were increased in the two groups,while the changes before and after treatment were significantly different(t =-2.911,-3.334,all P＜ 0.05).The EF D-value of the two groups was (4.59 ± 8.48)％ before treatment and was (9.00 ± 7.14)％ after treatment,which were not significantly different(P ＞ 0.05).FS was higher compared with pre-treatment in FS reduction group(FS ＜ 25％) and the changes before and after treatment[(19.75 ± 2.88)％,(21.92 ± 5.67)％] were significantly different(t =-2.297,P ＜ 0.05).Conclusions This study shows that the feasibility of clinical treatment of patients with CKD is very promising.The treatment of fixed prescription is effective.

Effect of peroxisome proliferator activated receptor γ agonist on angiotensin converting enzyme 2 mRNA expression in monocyte-derived macrophages of essential hypertensive patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effect of peroxisome proliferator activated receptor γ (PPAR-γ) agonist on the angiotensin converting enzyme 2 (ACE2) mRNA expression in monocyte-derived macrophages of essential hypertensive patients.</p><p><b>METHODS</b>Totally 57 essential hypertensive patients were randomly divided into three groups: conventional treatment group (n=18), telmisartan group (n=19), and benazepril group (n=20); 20 patients with normal blood pressure were also selected as the control group. Monocyte-derived macrophages were isolated from blood samples of patients in all four groups. The expression of ACE2 mRNA in monocyte-derived macrophages was detected by RT-PCR before treatment and 4 and 12 weeks after treatment.</p><p><b>RESULTS</b>Four and 12 weeks after treatment, the systolic pressure and diastolic pressure of telmisartan group and benazepril group were significantly lower than that of the conventional treatment group (all P<0.01), and the systolic pressure and diastolic pressure of telmisartan group were significantly lower than that of the benazepril group(both P<0.01) .The expression of ACE2 mRNA in monocyte-derived macrophages were significantly lower in essential hypertensive patients than that in control group (P<0.01). After having been treated for 4 weeks and 12 weeks, the expression of ACE2 mRNA in monocyte-derived macrophages of hypertensive patients in telmisartan and benazepril groups were significantly higher than that in conventional treatment group (all P<0.01), and the expression of ACE2 mRNA in telmisartan group was significantly higher than that in benazepril group (both P<0.01).</p><p><b>CONCLUSION</b>PPAR-γ agonist could increase the ACE2 mRNA expression in monocyte-derived macrophages of essential hypertensive patients.</p>

Effects of alpha-linolenic acid on inflammation and oxidative stress in the diabetic rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of alpha-linolenic acid (ALA) on inflammation and oxidative stress in the diabetic rats.</p><p><b>METHODS</b>An experimental type 2 diabetes mellitus model was induced by feeding male SD rats with diet of high fat for 4 weeks and then injected them intraperitoneally with streptozocin (STZ) at 30 mg/kg. Then the animals were randomly divided into three groups (n = 10): control group, diabetic group and ALA group. Four weeks later, tumor necrosis factor (TNF)-a, soluble P-selectin (sP-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), nitric oxide (NO) production, malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in the serum were determined.</p><p><b>RESULTS</b>Inflammatory agents including TNF-alpha, sP-selectin and sICAM-1 increased in diabetic rats to compare with control group. Treatment with ALA significantly decreased TNF-alpha, sP-selectin and slCAM-1 to compare with diabetic group. Furthermore, compared with control group, serum MDA production increased whereas NO production, SOD and CAT activities decreased in diabetic rats. Treatment with ALA reduced MDA production, increased NO production, promoted SOD and CAT activities compared with diabetic group.</p><p><b>CONCLUSION</b>These results indicate that diet rich in ALA exerted the anti-inflammatory and anti-oxidative effects in diabetic rats, which may be beneficial to the prevention and treatment of diabetes.</p>

Polymorphisms in the glutathione peroxidase-1 gene associated with increased risk of Keshan disease / 中华预防医学杂志

<p><b>OBJECTIVE</b>To assess the association of blood selenium and polymorphism of glutathione peroxidase-1 (GPx-1) genes in patients with Keshan Disease (KD) and provide genetic evidence for KD susceptibility.</p><p><b>METHODS</b>The levels of whole blood selenium and the activity of GPx-1 were measured with spectrophotometric and enzymatic method among 71 KD patients and 290 controls (including 78 internal controls and 212 external controls). The genotype of GPx-1 at 198 site was analyzed by sequencing and PCR-RFLP. The functions of two GPx-1 variants were studied by rat neonatal cardiomyocytes transfection and expression plasmid.</p><p><b>RESULTS</b>Blood level of selenium in KD patients was (0.8 ± 0.2) µmol/L, the internal controls' was (0.9 ± 0.2) µmol/L, and the external controls' was (1.2 ± 0.2) µmol/L (F = 4.888, P < 0.001).GPx-1 activity of KD patients was (73.0 ± 12.6) × 10(-10)U/RBC, internal controls' was (80.9 ± 9.2) × 10(-10)U/RBC, and external controls' was (115.8 ± 21.1) × 10(-10)U/RBC (F = 5.324, P < 0.001). Those of KD patients were significantly lower than controls. The polymorphism (Pro198Leu) of GPx-1 were identified; the frequency of Pro198Leu of KD patients was 21.1%, the frequency of controls was 10.7% (χ(2) = 5.588, P = 0.018). The level of blood selenium in variant subgroup (Pro198Leu or Leu198Leu) was (0.9 ± 0.2) µmol/L, and its in non-variant subgroup was (1.1 ± 0.3) µmol/L (t = 3.183, P < 0.01); The GPx-1 activity in variant subgroup was (86.1 ± 23.0) × 10(-10)U/RBC, and its in non-variant subgroup was (101.8 ± 25.9) × 10(-10)U/RBC (t = 5.784, P < 0.01). Further analysis revealed a synergistic-multiplicative interaction between presence of GPx-1 codon198 alleles and low blood selenium level. Over-expression of GPx-1 (198Leu) in rat cardiomyocytes caused 30% lower enzyme activity and less response to increasing concentrations of selenium than with over-expression of GPx-1 (198Pro).</p><p><b>CONCLUSION</b>Low blood selenium in carriers with the 198Leu-susceptible genotype of GPx-1 is associated with low GPx-1 activity, synergistic-multiplicative interaction was found between these two factors. And these two factors may increase the risk of KD.</p>

Binding activity of polypeptide containing human Na+, K+-ATPase alpha1 subunit M1-M2 extracellular segment / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the binding activity of polypeptide containing human Na+, K+-ATPase alpha1 subunit M1-M2 extracellular segment (HES1 derivative).</p><p><b>METHODS</b>HES1 derivative was synthesized by Fmoc method and purified by high-performance liquid chromatography-mass spectrometry, and its binding activity was identified by radioligand binding assay.</p><p><b>RESULTS</b>3H-ouabain and synthetic HES1 derivative showed some binding activity with the equilibrium dissociation constant (KD) of 24.58 nmol/L, with the the receptor density of 492.43 fmol x mg(-1) pro. and IC50 of 3.078 x 10(-7) mol/L.</p><p><b>CONCLUSION</b>HES1 derivative can bind to ouabain and has the potential of becoming an effective therapeutic agent.</p>

Activity identification of peptide containing rat sodium pump α2 subunit M1-M2 extramembrane fragment in vitro / 生理学报

In order to explore the activity of a peptide containing rat sodium pump α2 subunit M1-M2 extramembrane fragment (RES2 derivative) in vitro, the peptide (Leu-Ala-Ala-Met-Glu-Asp-Glu-Pro-Ser-Asn-Asp-Asn-Gly-Gly-Gly-Ser) was synthesized by peptide synthesizer with Fmoc method and purified by high performance liquid chromatography (HPLC). Its binding activity was identified by radioligand-receptor binding assay (RRA) and its bioactivity was measured by erythrocyte (86)Rb uptake. The results of saturation binding experiment and competitive binding experiment showed that the synthesized RES2 derivative had the capability to bind to (3)H-ouabain. The dissociation constant (K(d)) was 38.46 nmol/L and IC(50) was 6.353 nmol/L. Erythrocyte (86)Rb uptake experiment showed that the RES2 derivative blocked the inhibitory effect of ouabain on the sodium pump on erythrocyte membrane in a dose-dependent manner. The results showed that the RES2 derivative is capable of binding to ouabain and improving the activity of sodium pump on erythrocyte membrane, suggesting that the RES2 derivative might become an effective antihypertensive drug in the future.

Arginine vasopressin stimulates proliferation of adult rat cardiac fibroblasts via protein kinase C-extracellular signal-regulated kinase 1/2 pathway / 生理学报

Arginine vasopressin (AVP), a neurohormone and hemodynamic factor implicated in the pathophysiology of hypertension and congestive heart failure, can also act as a growth-stimulating factor. Our previous work demonstrated that AVP is a mitogen for neonatal rat cardiac fibroblasts (CFs). In the present study, we extended our investigations to adult rat CFs to explore whether AVP could induce adult rat CF proliferation and, if so, to identify the mechanism involved. Adult rat CFs were isolated, cultured and subjected to AVP treatment. DNA synthesis and cell cycle distribution were analyzed by [(3)H]-thymidine incorporation and flow cytometry. Cellular extracellular signal-regulated kinase 1/2 (ERK1/2) activity was measured by in vitro kinase assay using myelin basic protein (MBP) as a substrate. Protein expressions of total- and phospho-ERK1/2, p27(Kip1), cyclins D1, A, E were assessed by Western blot. The results showed that AVP stimulated DNA synthesis in adult rat CFs, and the effect was abolished by a V1 receptor antagonist, d(CH(2))(5)[Tyr(2)(Me), Arg(8)]-vasopressin (0.1 μmol/L), but not by a V2 receptor antagonist, desglycinamide-[d(CH(2))(5), D-Ile(2), Ile(4), Arg8]-vasopressin (0.1 μmol/L). AVP induced an activation of ERK1/2, which could be mimicked by the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA, 30 nmol/L, 5 min), but abolished by depletion of PKC via chronic PMA incubation (2.5 μmol/L, 24 h). In addition, AVP down-regulated protein expression of p27(Kip1), increased protein expressions of cyclins D1, A and E, and induced cell cycle progression from G(0)/G(1) into S stage. Inhibition of ERK1/2 activation by PD98059 (30 μmol/L) abolished the effect of AVP on DNA synthesis, protein expressions of p27(Kip1), cyclins D1, A and E as well as cell cycle progression. These results suggest that AVP is also a growth factor for adult rat CFs. The mitogenic effect of AVP is mediated via V1 receptors and PKC-ERK1/2 pathway. Moreover, AVP modulates the expressions of cell cycle regulatory proteins p27(Kip1) and cyclins D1, A and E, which lie downstream of ERK1/2 activation, and induces cell cycle progression in adult rat CFs.

Sodium current kinetics of transitional myocytes in Koch triangle of rabbit hearts / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Few studies have explored the inward sodium current (INa) kinetics of transitional cardiomyocytes. This study aimed to explore the kinetics of transitional cardiomyocytes types alpha and beta.</p><p><b>METHODS</b>The whole-cell patch clamp technique was used to study the rapid INa of isolated transitional cardiomyocytes in the Koch triangle of rabbit hearts.</p><p><b>RESULTS</b>Maximal amplitude and density of INa in type alpha and type beta was (-1627 +/- 288) pA (alpha), (-35.17 +/- 6.56) pA/pF (beta) and (-3845 +/- 467) pA (alpha), (-65.64 +/- 10.23) pA/pF (beta) (P < 0.05). Steady state activation curves of INa, fitted to a Boltzmann distribution for both types, were sigmoid in shape. Half activation voltage and slope factors did not significantly differ between types at (-43.46 +/- 0.85) mV (alpha), (-41.39 +/- 0.47) mV (beta) or (9.04 +/- 0.66) mV (alpha), (11.08 +/- 0.89) mV (beta). Steady state inactivation curves of INa, fitted to a Boltzmann distribution in both types were inverse "S" shape. Half inactivation voltage and slope factors were (-109.9 +/- 0.62) mV (alpha), (-107.5 +/- 0.49) mV (beta) and (11.78 +/- 0.36) mV (alpha), (11.57 +/- 0.27) mV(beta), (P > 0.05), but time constants of inactivation were significantly different at (1.10 +/- 0.19) mV (alpha) and (2.37 +/- 0.33) ms (beta), (P < 0.05). Time constants of recovery from inactivation of INa for both types were (122.16 +/- 27.43) mV (alpha) and (103.84 +/- 28.97) ms (beta) (P < 0.05).</p><p><b>CONCLUSIONS</b>Transitional cardiomyocytes in rabbit hearts show a heterogeneous, voltage gated and time dependent fast inward sodium current. Types alpha and beta show the features of INa similar to those in slow- and fast-response myocytes, with probably better automaticity and conductivity, respectively.</p>

Inhibitory effects of rosiglitazone against endothelin-1-induced proliferation of rat cardiac myocytes: the role of PKC-c-fos pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of rosiglitazone (RSG, the activator of peroxisome proliferators activated receptor lambda) for inhibiting endothelin-1 (ET-1)-induced neonatal rat cardiac myocyte hypertrophy and the role of protein kinase C (PKC) and c-fos.</p><p><b>METHODS</b>In vitro cultured neonatal rat cardiac myocytes were treated with ET-1, phorbol ester (PMA, the PKC activator), ET-1+RSG, ET-1+chelerythrine (che, the PKC inhibitor), PMA+RSG, or without treatment (control), respectively. The effects of RSG on the protein content, (3)H-leucine incorporation, PKC activity and C-fos protein expression were observed in the cardiac myocytes stimulated with ET-1 or PMA.</p><p><b>RESULTS</b>After two days of culture, the intracellular protein content in ET-1 group and PMA group were increased by 15% (339-/+15 microg/ml) and 13% (329-/+14 microg/ml) as compared with the control cells (290-/+13 microg/ml), respectively (P<0.01). Compared with the ET-1 group, cells treated with ET-1+10(-8) mol/L RSG, ET-1+10(-7) mol/L RSG, and ET-1+che showed decreased intracellular protein content by 10% (303-/+14 microg/ml, P<0.05), 12% (292-/+11 microg/ml, P<0.05), and 13% (291-/+12 microg/ml, P<0.01), respectively. The intracellular protein content in PMA+10(-7) mol/LRSG group was decreased by 10% (P<0.05) in comparison with the PMA group. RSG inhibited protein synthesis enhancement and increased (3)H-leucine incorporation induced by ET-1 and PMA, and antagonized the effects of ET-1 and PMA in promoting PKC activity and c-fos protein expression in the myocytes.</p><p><b>CONCLUSION</b>The inhibitory effect of RSG on ET-1- or PMA-induced myocyte hypertrophy is associated with PKC-c-fos pathway.</p>

Measurement and analysis of blood plasma brain matriuretic peptide in Keshan disease patients / 中国地方病学杂志

Objective To investigate the relationship and clinical significance of blood plasma brain natriuretic peptide (BNP) and Keshan Disease (KD). Methods Seventy KD patients and 30 healthy volunteers in endemic area were investigated with Doppler Echocardiography for the measurement of left ventricular end-diastolic diameter(LVEDD) and left ventricular ejection fraction (LVEF), and the plasma BNP levels were determined with microparticle enzyme immunoassay. Results The BNP levels in plasma in KD patients [(444.61±102.31), (87.21±23.15)ng/L] were significantly higher than that of healthy volunteers [(34.91±15.21)ng/L],the differencesbeing statistical significant (q=39.74,5.82,P<0.01). The BNP levels in chronic KD patients were higher than that of latent KD patients (q=37.62,P<0.01). The plasma BNP levels in KD patients with LVEDD 60 nun [(928.80±134.27)ng/L] were significantly higher than those of patients with LVEDD 55～60 mm [(89.24±52.31)ng/L] and LVEDD<55 nun [(67.14±6.92)ng/L],the differencesbeing statistical significant (q=44.30,48.16, P<0.01), The plasma BNP levels in KD patients with LVEF<35%[(1654.21±421.35) ng/L] were significantly higher than those of patients with 35% ~ 50%[(421.54±112.32)ng/L] and50% [ (81.21±72.85 ng/L)], the differencesbeing statistical significant(q=24.91,72.66, P<0.01), The BNP levels in LVEF 35%～50% were higher than that of 50% (q=11.84,P<0.01). Conclusion The plasma BNP levels were important for the diagnosis, grouping, therapeutic effect and prognostic evaluation of KD.

The study on relation of HLA-DRB1 gene polymorphism to Keshan disease and its association and linkage in the core families / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate HLA-DRB1 gene polymorphism in patients with Keshan disease (KD) in the north of China, and its relation to KD in the core families.</p><p><b>METHODS</b>Polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method was used to determine HLA-DRB1 genotypes in 118 KD patients, including 63 with latent KD and 55 with chronic KD. Sixty-five normal from the same area were selected as controls. The haplotype based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT) methods were used to analyze the genetic association and linkage of HLA-DRB1 with KD in 18 KD core families.</p><p><b>RESULTS</b>(1) Thirteen kinds of alleles of HLA-DRB1 gene were found in all patients and the controls. (2) The distributive frequency of DR7 allele was significantly lower in chronic KD patients than that in controls (P< 0.01, OR is 0.1695). (3) The distributive frequency of DR7 allele was statistically lower in chronic KD (P< 0.01, OR is 0.091) and showed no differences in latent KD patients as compared with the controls. (4) DR15 allele of HLA-DRB1 gene showed significant association (chi square is 9.32, P< 0.01) and linkage (chi square is 7.40, P< 0.01) with KD patients in the core families.</p><p><b>CONCLUSION</b>The results show that there might be the genetic susceptibility in the pathogenesis of KD. DR7 allele of HLA-DRB1 gene might be the protective gene of KD. Patients with DR7 allele might be more difficult to become to chronic KD. DR15 allele of HLA-DRB1 gene might be linked to the susceptive site of KD.</p>

Quantitative connexin mRNA detection in posterior nodal extension of adult rat heart / 南方医科大学学报

<p><b>OBJECTIVE</b>To quantitatively detect the expression of connexins (Cx) mRNA in the posterior nodal extension (PNE) of adult rat heart and understand the relationship between Cx expression and atrial ventricular nodal reentrant tachycardia (AVNRT).</p><p><b>METHODS</b>PNE was separated from adult rat heart by means of laser microdissection (LCM), and the cells were also isolated from the atrioventricular node (AVN), sinoatrial node (SAN), Purkinje fiber (PF), right atrium (RA) and right ventricle (RV), to serve as the controls. The Cx mRNA level was detected in these cells with quantitative real-time PCR (QRT-PCR).</p><p><b>RESULTS</b>The cells were successfully isolated from the PNE and other regions of adult rat heart, where heterogeneous expression of the 3 Cx isoforms (Cx43, Cx45, and Cx40) were observed. Cx45 mRNA showed higher expression in the PNE than in the working myocardium, whereas Cx43 mRNA level was about 25 times higher (P<0.05) in the working myocardium and 18 times higher (P<0.05) in the PF than in the PNE. In the PF, Cx40 mRNA level was proximately 6.8 times (P<0.01) as much as that in the PNE. Cx expression in the PNE was, however, similar to that in the SAN and AVN.</p><p><b>CONCLUSION</b>Cx mRNAs exhibit heterogeneous expression in the PNE to allow the formation of the slow pathway. In addition, Cx expression in the PNE is very different from that in the adjacent myocardium, resulting in conduction discontinuity at the cellular junction, where, on certain occasion, unidirectional block may occur to cause AVNRT.</p>

Relationship between cardiomyocyte protein synthesis and cell viability / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the relationship between protein sythesis and cardiomyocyte viability in neonatal rats.</p><p><b>METHODS</b>The protein sythesis in neonatal rat cardiomyocytes was measured according to Brandford's method, the absorbance at 490 nm (A(490 nm)) of the cells was measured with MTT assay and the cell viability evaluated by the ratio of A(490 nm) to the total cell number.</p><p><b>RESULTS</b>ET-1 increased cardiomyocyte protein synthesis dose-dependently, and this effect was attenuated by the application of lacidipine and tetramethylpyrazines Higher doses of ET-1 resulted in lower A(490 nm)/total cell number ratio, which was further lowered by larcidipine and tetramethylpyrazine.</p><p><b>CONCLUSION</b>The status of protein synthesis is not associated with the viability of neonatal rat cardiomyocytes.</p>

Peroxisome proliferator-activated receptor activator troglitazone inhibits angiotensin II-stimulated secretion of vasoactive factors by endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand on angiotensin II (AngII)-induced endothelin-1 (ET-1) and NO secretion by endothelial cells in comparison with AngII type I receptor (AT1R) antagonist losartan, so as to reveal the relationship between PPAR gamma and essential hypertension.</p><p><b>METHODS</b>Cultured human umbilical vein endothelial cells (HUVECs) were treated with AngII, PPAR gamma ligand troglitazone, AngII plus troglitazone, and AngII plus AT1R antagonist losartan, respectively, and the concentrations of NO and ET-1 in the cell culture supernatant were measured to evaluate the effects of troglitazone and losartan on AngII-induced NO and ET-1 production by human endothelial cells.</p><p><b>RESULTS</b>Treatment of the HUVECs with troglitazone at 10 micromol/L and 50 micromol/L did not produce significant changes in ET-1 concentration in the cell culture supernatants, but significantly increased NO concentration as compared with the control group (P<0.05). Triglitazone at the concentration of 50 micromol/L significantly inhibited AngII (1x10(-6) mol/L)-induced ET-1 production (P<0.05), and at both 10 and 50 micromol/L, troglitazone inhibited the NO release-lowering effect of AngII in the endothelial cells (P<0.05). Both troglitazone and losartan inhibited AngII-induced ET-1 production by the endothelial cells, but losartan showed more potent effect (P<0.05). Similarly, both troglitazone and losartan inhibited decreased NO production in response to AngII treatment, and again losartan showed stronger effect (P<0.05).</p><p><b>CONCLUSION</b>PPAR gamma ligand troglitazone can inhibit AngII-induced ET-1 production enhancement and decreased NO release by the endothelial cells, but its effect is not so strong as losartan, suggesting that troglitazone modulates blood pressure not solely through AT1R pathway.</p>

Morphological and electrophysiological properties of single myocardial cells from Koch triangle of rabbit heart / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The morphological and electrophysiological characteristics of cardiac cells in Koch triangle are still disputed. We studied the appearance and electrical properties of these diverse myocytes to elucidate their complex electrophysiological phenomena.</p><p><b>METHODS</b>Experiments were conducted using cooled charge coupling device (CCD) system and whole cell, patch clamp technique to determine the morphology, action potential and sodium current density of single viable myocytes enzymatically isolated from the Koch triangle of rabbit hearts.</p><p><b>RESULTS</b>Morphologically, cardiac cells in shape of spider, tiny spindle, slender spindle, rod and strip were observed in percentage of 3.0 +/- 0.3, 35.0 +/- 5.0, 15.0 +/- 2.0, 40.0 +/- 5.0 and 6.0 +/- 0.7 respectively. The cellular dimensions and capacitance gradually increased in the above order (all P < 0.05). Electrophysiologically, action potential configurations recorded from them were similar respectively to nodal (N), atrial nodal (AN), nodal Hisian (NH), atrial (A) and Hisian like potentials obtained from the intact atrioventricular nodal preparations. Diastolic depolarization appeared in all myocytes except for rod cells. Sodium current density increased in the order of tiny spindle, strip, rod, slender spindle cell (all P < 0.05), but could not be detected in spider-shaped cells. Linear regression analysis revealed that membrane capacitance was correlated negatively to the rate of diastolic depolarization r = -0.70, P < 0.001, but positively to maximum depolarization potential, amplitude of action potential, upstroke velocity and maximum peak value of sodium current density r = 0.84, 0.80, 0.87 and 0.75, respectively; all P < 0.001.</p><p><b>CONCLUSIONS</b>The results demonstrated that spider-shaped, spindle, rod and strip cells in Koch triangle might correspond to pacemaking, transitional, atrial and Purkinje like cells, respectively. Furthermore, tiny spindle and slender spindle cells were referred to transitional cell alpha (TCalpha) and beta (TCbeta) accordingly considering their distinctive electrical properties. Different myocytes with diverse electrical properties constituted the infrastructure of sophisticated electrophysiological phenomena in Koch triangle. In view of the prominent percentage and electrical properties, tiny spindle and slender spindle cells were presumed to play important roles.</p>

Effect of shenmai injection on immunologic function in patients with dilated cardiomyopathy / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of Shenmai Injection (SMI) on immunologic function in patients with dilated cardiomyopathy (DCM).</p><p><b>METHODS</b>Fifty-six patients were divided into two groups, the control group treated with conventional western medicine, and the SMI group treated with conventional western medicine plus SMI. The indices including red blood cell (RBC) C3b receptor rosette (RBC-C3bRR) and immune complex rosette (RBC-ICR), T-lymphocyte subsets (CD3, CD4, CD8, CD4/CD8) were determined before and after treatment.</p><p><b>RESULTS</b>The level of RBC-C3bRR, CD4, CD8 and CD3 in patients with DCM were significantly decreased (P <0 .01, P < 0.05), RBC-ICR and CD4/CD8 were significantly increased than those in the normal control group (P < 0.01); While the level of RBC-C3bRR, CD4, CD8 and CD3 in the SMI group after treatment were significantly higher, and the level of RBC-ICR and CD4/CD8 were significantly lower (P < 0.01, P < 0.05) than those in the control group.</p><p><b>CONCLUSION</b>The RBC immune adherence and cellular immune function are lower in patients with DCM, and SMI has the effect in regulating immune function in patients with DCM.</p>

Morphological and electrophysiological study on the inferior nodal extension and transitional cellular band in the rabbit atrioventricular junctional area / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Advances in catheter ablation procedures for the treatment of supraventricular arrhythmias have created the need to understand better the morphological and electrophysiological characteristics of the inferior nodal extension (INE) and transitional cellular band (TCB) in the atrioventricular (AV) junctional area.</p><p><b>METHODS</b>Firstly, we observed the histological features of 10 rabbit AV junctional areas by serial sections under light microscopy. Then we recorded the action potentials (APs) of transitional cells (TCs) in the INE, TCBs, AV node, and ordinary right atrial myocytes from the AV junctional area of 30 rabbits using standard intracellular microeletrode techniques.</p><p><b>RESULTS</b>Under light microscopy, the INE appeared to be mostly composed of transitional cells linking upward to the AV node. Four smaller TCBs originated in the orifice of the coronary sinus, the region between the septal leaflet of the tricuspid valve and the coronary sinus, the inferior wall of the left atrium, and the superior interatrial septum, respectively, all linking to the INE or the AV node. Compared with ordinary atrial myocytes, the AP of the TCs in both the INE and the TCBs had a spontaneous phase 4 depolarization (not present in ordinary atrial myocytes), with a less negative maximum diastolic potential, a smaller amplitude, a slower maximum velocity of AP upstroke, and a longer action potential duration at 50% repolarization (APD50) and at 30% repolarization (APD30). The AP characteristics of these TCs were similar to those of the AV node, except that the velocities of the phase 4 spontaneous depolarization were slower and their action potential durations at 90% repolarization (APD90) were shorter. Moreover, APD50 and APD30 of the TCs of the TCBs were shorter than in the case of TCs of the AV node.</p><p><b>CONCLUSIONS</b>The TCs of the INE and TCBs are similar to slow response automatic cells. They provide a substrate for slow pathway conduction. In addition, repolarization heterogeneity exists in the AV junctional area.</p>