ABSTRACT
The objective was to investigate the effects of valsartan on the electrophysiological characteristics of left ventricular hypertrophic myocardium in spontaneously hypertensive rats (SHR). A total of 24 10-week-old male SHR were divided into two groups: valsartan and non-valsartan groups (n=12 in each). Twelve 10-week-old Wistar-Kyoto rats were served as the control group. Kv4.2 expression was measured in left ventricular myocardium using western blots. In addition, the systolic blood pressure, left ventricular mass index (LVMI), ventricular effective refractory period and ventricular fibrillation threshold (VFT) were also measured after eight weeks. INa, ICaL, Ito and membrane capacitance were measured in left ventricular myocytes after 8 weeks by whole-cell patch clamp. Valsartan decreased LVMI compared with the non-Valsartan group (Valsartan vs. non-Valsartan: 3.2±0.03 mg g(-1) vs. 3.7±0.02 mg g(-1), P<0.01). Valsartan also enhanced the VFT compared with the non-Valsartan group (Valsartan vs. non-Valsartan: 18.6±0.3 mA vs. 15.4±0.4 mA, P<0.01). The expression of Kv4.2 was significantly lower in the non-Valsartan and Valsartan groups compared with the control group (P<0.01). The expression of Kv4.2 was significantly higher in the Valsartan group compared with the non-Valsartan group (P<0.01). Valsartan decreased the density of ICaL compared with non-Valsartan group (Valsartan vs. non-Valsartan: -5.5±0.6 pA/pF vs. -7.2±0.9 pA/pF, P<0.05). Valsartan improved the density of Ito compared with non-Valsartan group(Valsartan vs. non-Valsartan: 13.93±0.8 pA/pF vs. 11.22±1.0 pA/pF, P<0.05). Valsartan improves the electrophysiological characteristics of left ventricular hypertrophic myocardium in spontaneously hypertensive rat.
Subject(s)
Blood Pressure/drug effects , Heart Ventricles/drug effects , Hypertrophy, Left Ventricular/physiopathology , Myocardium/metabolism , Tetrazoles/pharmacology , Valine/analogs & derivatives , Animals , Heart Ventricles/metabolism , Heart Ventricles/physiopathology , Hypertrophy, Left Ventricular/metabolism , Male , Rats , Rats, Inbred SHR , Shal Potassium Channels/metabolism , Valine/pharmacology , ValsartanABSTRACT
<p><b>OBJECTIVE</b>To investigate the inhibitory effects of AP-1 decoy oligodeoxynucleotides (ODNs) on angiotensin II (AngII)-induced proliferation and collagen synthesis in neonatal rat cardiac fibroblasts (CFs).</p><p><b>METHODS</b>The CFs of neonatal SD rats were cultured in serum-free medium for 24 h and stimulated with 10(-7) mol/L AngII in the presence of AP-1 decoy ODNs or mutational AP-1 decoy ODNs at varied concentrations. MTT assay was employed for quantitative evaluation of the CF proliferation. Collagen synthesis in the CFs was assessed with hydroxyproline, and the cell cycle distribution determined with flow cytometry (FCM).</p><p><b>RESULTS</b>With the increase of the concentration of AP-1 decoy ODNs, the absorbance at 490 nm (OD490) of the CFs decreased gradually as shown by MTT assay. Treatment with 100 or 200 nmol/L AP-1 decoy ODNs resulted in significantly lowered OD490 of the CFs as compared with that of AngII group. The concentration of hydroxyproline increased significantly after treatment with 10(-7) mol/L AngII in comparison with the control group (P<0.05). Hydroxyproline concentration in cells treated with 100 or 200 nmol/L AP-1 decoy ODNs was significantly lower than that in the 10(-7) mol/L AngII-treated cells. AP-1 decoy ODNs decreased the cell percentage in S phase and increased hydroxyproline concentration, but increased the percentage of cells in G0/G1 phase. AP-1 decoy ODNs at 100 and 200 nmol/L did not obviously affect AngII-induced CF proliferation and collagen synthesis (P<0.01).</p><p><b>CONCLUSION</b>AP-1 decoy can inhibit AngII-induced rat CF proliferation and collagen synthesis possibly by affecting the cell cycle distribution.</p>
Subject(s)
Animals , Rats , Angiotensin II , Pharmacology , Animals, Newborn , Cell Cycle , Cell Proliferation , Cell Survival , Cells, Cultured , Collagen , Dose-Response Relationship, Drug , Fibroblasts , Cell Biology , Metabolism , Flow Cytometry , Mutation , Myocardium , Cell Biology , Metabolism , Oligodeoxyribonucleotides , Genetics , Pharmacology , Rats, Sprague-Dawley , Transcription Factor AP-1 , GeneticsABSTRACT
Objective To investigate the effects of activator protein-1(AP-1)decoy oligodeoxynucleotides (ODNs)on the myocardial fibrosis induced by angiotension Ⅱ(Ang Ⅱ)in vitro.Methods CFs of neonatal Spra- gue-Dawley(SD)rats were isolated by trypsin digestion method.CFs were co-cultured with 10~(-7)mol/L Ang Ⅱ in the presence of different concentration of activator protein-1(AP-1)decoy ODNs or mutational AP-1 decoy ODNs for 24 h.Collagen synthesis was assessed by hydroxyproline and the mRNA expression of collagen Ⅰ,collagen Ⅲ.Results The concentration of hydroxyproline increased significantly after treated by 10~(-7)mol/L Ang Ⅱ;decoy ODNs on the range of 10-200 nmol/L dose dependently decrease synthesis of collagen;Ang Ⅱ stimulates mRNA expression of collagen Ⅲ(1.04?0.07 vs 1.63?0.071,n=3,P
