1.Effect between felodipine plus irbesartan and felodipine plus metoprolol regimen on the sexual function in young and middle-aged women with hypertension.
Dian XU ; Jing YU ; Pei-Jun LIU ; Xue-Ya GUO ; Hao HU ; Peng CHANG ; Feng ZHAO ; Xiu-Li LI ; Xue-Hong CHEN ; Xi-Ping SHEN ; Yi ZHANG ; Feng BAI
Chinese Journal of Cardiology 2010;38(8):728-733
OBJECTIVETo compare the effects between felodipine plus irbesartan and felodipine plus metoprolol regimen on blood pressure and the sexual function in young and middle-aged hypertensive women.
METHODSIn this prospective, randomized, parallelized, controlled and fixed combined therapy trial, 99 female patients (aged 18 to 60) with grade 1 and grade 2 hypertension (BP ≥ 140/90 mm Hg and < 179/109 mm Hg, 1 mm Hg = 0.133 kPa) were assigned to felodipine 5 mg q.d + irbesartan 150 mg q.d (F + I group, n = 49) and felodipine 5 mg q.d + metoprolol 47.5 mg q.d (F + M group, n = 50) group. Target blood pressure was < 140/90 mm Hg. The female sexual function index (FSFI) questionnaire, levels of serum estradiol and testosterone were assessed. Female sexual dysfunction was defined as a FSFI score of less than 25.5. Patients were followed up for 24 weeks.
RESULTSThe rate of achieving blood pressure goal between 2 groups was similar at the 4th, 8th, 12th and 24th weeks respectively (42.9% vs. 62.0% at 4th week, 89.8% vs. 90.0% at 8th week, 93.9% vs. 94.0% at 12th week, 98.0% vs. 96.0% at 24th week, P > 0.05). Compared to baseline, scores for the items related to "desire" and "arousal" were significantly improved (P < 0.05), the level of the serum estradiol was significantly elevated [(50.3 ± 37.4) pg/L vs. (54.4 ± 10.8) pg/L before menopause, (18.4 ± 2.9) pg/L vs. (20.2 ± 3.1)pg/L after menopause, P < 0.05] and the level of the serum testosterone was significantly decreased [(722.8 ± 277.1) ng/L vs. (650.0 ± 156.0) ng/L before menopause, (841.2 ± 279.3) ng/L vs. (761.9 ± 197.8) ng/L after menopause, P < 0.05] in the F + I group, while scores for the items related to "sexual desire" and "lubrication" were statistically reduced (P < 0.01), the concentration of the serum estradiol was significantly reduced [(57.4 ± 9.7) pg/L vs. (51.1 ± 12.1) pg/L before menopause, (19.8 ± 2.3) pg/L vs. (17.8 ± 3.3) pg/L after menopause, P < 0.01] and the level of the serum testosterone was significantly increased [(775.6 ± 217.8) ng/L vs. (886.0 ± 186.4) ng/L before menopause, (812.5 ± 311.3) ng/L vs. (914.4 ± 300.2) ng/L after menopause, P < 0.01] in the F + M group. FSFI score was negatively correlated with age and systolic blood pressure levels.
CONCLUSIONfelodipine plus irbesartan or metoprolol for 24 weeks equally reduced blood pressure and the former regimen is superior to the latter on sexual function improvement in this patient cohort.
Adolescent ; Adult ; Antihypertensive Agents ; therapeutic use ; Biphenyl Compounds ; pharmacology ; therapeutic use ; Felodipine ; pharmacology ; therapeutic use ; Female ; Humans ; Hypertension ; drug therapy ; Metoprolol ; pharmacology ; therapeutic use ; Middle Aged ; Prospective Studies ; Sexual Dysfunction, Physiological ; Tetrazoles ; pharmacology ; therapeutic use ; Young Adult
2.The effect of angiotensin II type 1 receptor blocker valsartan in preventing hepatic fibrosis induced by dimethylnitrosamine in rats.
Feng-jun SHEN ; Yue-ke ZHU ; Ji-dong JIA ; Hong MA ; Bao-en WANG
Chinese Journal of Hepatology 2004;12(10):605-608
OBJECTIVETo observe the effects of angiotensin II type 1 receptor blocker valsartan in preventing hepatic fibrosis induced by dimethylnitrosamine in rats.
METHODSExcept rats in the control group, all were given intraperitoneal injections of 1% dimethylnitrosamine (DMN 1 ml/kg, two or three consecutive days/a week for 6 weeks). From the first day of the intraperitoneal injection, rats in treatment groups were given valsartan for 8 weeks by gastric gavage. Liver tissue and blood samples of all rats were examined at 56 days (8 weeks). AngII levels were determined by radioimmunoassay. Hepatic mRNA levels of Collagen type I (Col I) and tissue inhibitor of metalloproteinase1 (TIMP1) were evaluated by reverse-transcription polymerase chain reaction (RT-PCR).
RESULTSValsartan significantly attenuated the degree of liver fibrosis and decreased the hepatic AngII content compared with DMN treated rats (P<0.01). mRNA levels of Col I and TIMP1 were upregulated in DMN treated rats compared with normal rats. Valsartan downregulated the elevation of Col I and TIMP1 mRNA levels (P<0.01).
CONCLUSIONHepatic AngII content of the model group was increased, the local tissue RAS was activated in DMN induced liver fibrosis. Valsartan can retard the progression of hepatic fibrosis and may provide an effective new strategy for anti-liver fibrosis therapy.
Angiotensin II Type 1 Receptor Blockers ; pharmacology ; therapeutic use ; Animals ; Dimethylnitrosamine ; Female ; Liver Cirrhosis, Experimental ; chemically induced ; prevention & control ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Tetrazoles ; pharmacology ; therapeutic use ; Valine ; analogs & derivatives ; pharmacology ; therapeutic use ; Valsartan
3.Clinical study of western medicine combined with Chinese medicine based on syndrome differentiation in the patients with polarized hypertension.
Song-lin CHEN ; Xiao-yun LIU ; Wen-ming XU ; Wei-yi MEI ; Xiao-lian CHEN
Chinese journal of integrative medicine 2012;18(10):746-751
OBJECTIVETo investigate the effects and safety of Western medicine combined with Chinese medicine (CM) based on syndrome differentiation in the treatment of elderly polarized hypertension (PHPT), or isolated systolic hypertension with low diastolic blood pressure (DBP).
METHODSA total of 125 elderly patients with PHPT were randomly assigned to two groups: 59 in the control group treated by Western medicine and 66 in the intervention group treated by Western medicine combined with CM treatment. Based on syndrome differentiation, the patients in the intervention group were further divided into subgroups of yang-qi deficiency and yin-qi deficiency. All subjects were treated with Western medicine of Amlodipine Besylate Tablets and Irbesartan Tablets (or Irbesartan and Hydrochlorothiazide Tablets), to decrease their systolic blood pressure (SBP) slowly to 125-135 mm Hg in 2-6 weeks. In the intervention group, Shiyiwei Shenqi Capsule was given additionally to the subgroup of yang-qi deficiency at the dosage of 3-5 capsules, thrice a day, while Dengzhan Shengmai Capsule was given additionally to the subgroup of yin-qi deficiency at the dosage of 2 capsules, 2-3 times per day. For all subjects, SBP, pulse pressure (PP), and DBP were measured before treatment and at the terminal of a 6-week treatment. For subjects in the intervention group, left ventricular ejection fraction (LVEF) was also recorded.
RESULTSAfter a 6-week treatment, the SBP in the two groups and the PP in the intervention group decreased significantly compared to those before treatment (P<0.05), while the PP in the control group showed no significant difference between prior and post-treatment (P>0.05). After treatment, the DBP in the control group decreased (P>0.05), while the DBP and LVEF in the intervention group showed an increase tendency although it had no statistical significance (P>0.05). When subjects in the intervention group were classified further by the course of disease, the DBP and LVEF of subjects whose course of disease were less than 2 years, increased significantly after treatment (P<0.05).
CONCLUSIONWestern medicine combined with CM treatment based on syndrome differentiation was safer and more effective than Western medicine alone in the treatment of elderly PHPT, because it not only reduced SBP but also improved DBP, which might lower the incidence of the cardiovascular and cerebrovascular events.
Aged ; Amlodipine ; adverse effects ; pharmacology ; therapeutic use ; Antihypertensive Agents ; adverse effects ; pharmacology ; therapeutic use ; Biphenyl Compounds ; adverse effects ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Diastole ; drug effects ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Stroke Volume ; drug effects ; Syndrome ; Tetrazoles ; adverse effects ; pharmacology ; therapeutic use
4.Studying the influence of Candesartan cilexetil on the lung fibrosis in rats exposed to silica.
Gang YIN ; Wei-Yong ZHU ; Hua ZHANG ; Yue-Fan LI ; Chun-ling ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2012;30(4):250-254
OBJECTIVETo explore the effects of Candesartan cilexetil on the rats exposed to silica.
METHODNinety-six wistar rats were randomly divided into model-group, intervention-group and control-group (32 rats a group). The intervention-group, model-group and control group were orally exposed to Candesartan cilexetil (10 mg/kg) and normal solution for a week, respectively. Then the model and intervention groups were exposed to silica by intratracheal infusion of silica dust suspension (50 mg/ml), the control group was exposed to 0.5 ml normal solution for 2 days. On the 3rd, 7th, 14th and 28th days after exposure to silica, 8 rats of each group were sacrificed, respectively. The samples of lung tissues were collected. The lung/body coefficients were detected. The pathological examinations were performed by HE and Masson staining. The levels of ACE in the lung tissues were observed by immunochemistry staining. The levels of TGF-β1 and Ang II in the BALF were examined by ELISA.
RESULTSOn the 3rd, 7th, 14th and 28th days after exposure, the levels of alveolitis and pulmonary fibrosis in the intervention group were significantly alleviated as compared with model group, and the lung/body coefficients in the intervention group, which were significantly lower than those in model group respectively (P < 0.01). As compared with control group, the levels of TGF-β1 and Ang II of the BALF in the model and intervention groups significantly enhanced (P < 0.01). As compared with model group, the levels of TGF-β1 and Ang II of the BALF in the intervention group significantly decreased (P < 0.01). As compared with control group, the levels of ACE of the lung tissues in the model and intervention groups significantly increased (P < 0.01). But the level of ACE of the lung tissues in the intervention group was significantly lower than that in the model group (P < 0.01).
CONCLUSIONThe early Candesartan cilexetil intervention could significantly decrease the levels of alveolitis and lung fibrosis, declined the levels of TGF-β(1) and Ang II of BALF and downregulated the expression level of ACE in lung tissues in rats exposed to silica.
Angiotensin II ; metabolism ; Animals ; Benzimidazoles ; pharmacology ; therapeutic use ; Bronchoalveolar Lavage Fluid ; Female ; Lung ; drug effects ; pathology ; Male ; Pulmonary Fibrosis ; chemically induced ; drug therapy ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity ; Tetrazoles ; pharmacology ; therapeutic use ; Transforming Growth Factor beta1 ; metabolism
5.On angiotensin II receptor distribution after myocardial infarction in dogs.
Xiu-fen QU ; Jing-jie LI ; Yang XI ; Jing-xia SHEN ; Chun-hong XIU ; Le YUE ; Gui-zhao WANG ; Yong-lin HUANG
Chinese Journal of Cardiology 2009;37(4):358-362
OBJECTIVETo investigate the effects of valsartan on expression of angiotensin II receptors in different regions of heart after myocardial infarction (MI).
METHODSCanines were divided into sham-operated control group (n=7), infarction group (n=7) and Valsartan group (10 mg x kg(-1) x day(-1) for 4 weeks after MI operation, n=7). Four weeks after operation, Doppler tissue imaging (DTI) was used to evaluate regional ventricular function in the noninfarcted myocardium (apical and basal near to the infarction region). The mRNA and protein expressions of angiotensin II type 1 receptor (AT1-R) and angiotensin II type 2 receptor (AT2-R) on the corresponding regions were detected by competitive reverse-transcriptase polymerase chain reaction technique and immunohistochemical technique respectively. Results The protein and mRNA expressions of AT1-R were significantly increased in both apical and basal regions near to the infarction in dogs with MI compared with those in control group (P < 0.05) which could be downregulated by valsartan (P < 0.05). AT2-R expressions were significantly upregulated in infarction group in both apical and basal regions compared with those in control group and valsartan further increased AT2-R expressions in both areas (P < 0.05). Myocardial peak systolic velocity (Sm), myocardial peak early diastolic velocity (Em) and myocardial peak late diastolic velocity (Am) at both apical and basal regions near to the infarction regions were significantly lower in MI group than those in the control group which could be significantly improved by valsartan.
CONCLUSIONBoth mRNA and protein expressions of AT1-R and AT2-R are upregulated in noninfarcted regions near MI, valsartan improved myocardial function via inhibiting AT1-R upregulation and enhancing AT2-R upregulation.
Angiotensin II Type 1 Receptor Blockers ; pharmacology ; therapeutic use ; Animals ; Dogs ; Female ; Male ; Myocardial Infarction ; drug therapy ; metabolism ; physiopathology ; Myocardium ; metabolism ; RNA, Messenger ; metabolism ; Receptor, Angiotensin, Type 1 ; metabolism ; Receptor, Angiotensin, Type 2 ; metabolism ; Tetrazoles ; pharmacology ; therapeutic use ; Valine ; analogs & derivatives ; pharmacology ; therapeutic use ; Valsartan
6.Preventive effect of low-dose carvedilol combined with candesartan on the cardiotoxicity of anthracycline drugs in the adjuvant chemotherapy of breast cancer.
Liang LIU ; Zhao-zhe LIU ; Yong-ye LIU ; Zhen-dong ZHENG ; Xue-feng LIANG ; Ya-ling HAN ; Xiao-dong XIE
Chinese Journal of Oncology 2013;35(12):936-940
OBJECTIVETo investigate the effect of low-dose carvedilol combined with candesartan in the prevention of acute and chronic cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.
METHODSForty patients were randomly divided into two groups: the experimental group with chemotherapy plus low-dose carvedilol combined with candesartan (20 cases) and control group with chemotherapy alone (20 cases). The same chemotherapy was given to the two groups. All the 40 patients had no contraindication for carvedilol and candesartan. Patients of the experimental group received low-dose carvedilol from 2.5 mg orally twice a day at first cycle to 5 mg twice a day gradually if no side reactions, and candesartan 2.5 mg orally once a day. Electrocardiogram, ultrasonic cardiogram, arrhythmia, troponin and non-hematologic toxicity were recorded and compared after the second, forth and sixth cycle of chemotherapy. Each cycle included 21 days.
RESULTSLVEF was decreased along with the prolongation of chemotherapy in the experimental group and control group. LVEDD and LVESD showed no significant changes in the experimental group, but gradually increased in the control group. After four and six cycles of chemotherapy, LVEF were (57.00 ± 5.13)% and (45.95 ± 3.68)%, respectively, in the control group, significantly lower than that of (67.00 ± 5.13)% and (57.50 ± 2.57)%, respectively, in the experimental group (P < 0.05). After six cycles of chemotherapy, LVEDD and LVESD were (50.00 ± 10.48) mm and (35.01 ± 2.99) mm, respectively, in the control group, significantly higher than those before chemotherapy (P < 0.05) and experimental group (P < 0.001). The rate of ST segment and T wave abnormalities was 80.0% in the control group after six cycles of chemotherapy, significantly higher than that of 25.0% after four cycles of chemotherapy (P = 0.001) and 10.0% after two cycles of chemotherapy (P < 0.001). The reduction of QRS voltage, arrhythmia and abnormal troponin were 55.0%, 45.0% and 45.0%, respectively, in the control group, significantly higher than those in the experimental group (20.0%, P < 0.05), (10.0%, P = 0.010) and (10.0%, P < 0.05), respectively. The rate of abnormal expression of troponin was 45.0% in the control group, significantly higher than the 10.0% in the experimental group (P < 0.05).
CONCLUSIONSThe use of low-dose carvedilol combined with candesartan can reduce the acute and chronic cardiotoxicity of anthracycline drugs, and with tolerable toxicities. This may provide a new approach to prevent cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.
Adrenergic beta-Antagonists ; administration & dosage ; pharmacology ; Adult ; Aged ; Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Arrhythmias, Cardiac ; chemically induced ; Benzimidazoles ; administration & dosage ; pharmacology ; Breast Neoplasms ; drug therapy ; surgery ; Carbazoles ; administration & dosage ; pharmacology ; Chemotherapy, Adjuvant ; Cyclophosphamide ; adverse effects ; therapeutic use ; Electrocardiography ; drug effects ; Epirubicin ; adverse effects ; therapeutic use ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Humans ; Mastectomy, Radical ; Middle Aged ; Propanolamines ; administration & dosage ; pharmacology ; Stroke Volume ; drug effects ; Tetrazoles ; administration & dosage ; pharmacology ; Troponin ; metabolism
7.Effect of valsatan on hepatocyte growth factor in the airways of asthmatic rats.
Chinese Journal of Contemporary Pediatrics 2006;8(6):482-485
OBJECTIVETo study the effect of valsatan (angiotensin II receptor antagonist, AT1) on hepatocyte growth factor (HGF) in the airways and airway remodeling in asthmatic rats.
METHODSThirty two rats were randomly assigned into A-D four groups. Group A was normal control without treatment. Groups B-D were challenged by ovalbumin (OVA) for 2 weeks, 4 weeks and 4 weeks respectively to induce asthma. Group D received intragastric administration of valsatan (30 microg/kg daily for 4 weeks) after OVA challenge. The expressions of HGF, angiotonin II (AngII) and transforming growth factor (TGF-beta1) in the airways were detected by immunihistochemical staining. The pathological changes of airways were observed by Haematoxylin and Eosin staining.
RESULTSThe HGF expression of Group B was significantly higher than that of Group A (10.69 +/- 0.96% vs 5.49 +/- 1.34%; P < 0.05). Group C also showed an increased HGF level (11.85 +/- 0.87%) compared with Group A (P < 0.05). The HGF level in Group D (15.58 +/- 1.06%) was significantly higer than that of both Group B and Group C (P < 0.05). The expressions of TGF-beta1 and AngII increased with the challenged time, while valsatan treatment decreased significantly the levels of both. Valsatan treatment attenuated airway injuries of asthmatic rats induced by OVA sensitization/challenge.
CONCLUSIONSHGF has protective effects on airways and anti-fibrotic effects. Valsatan can improve airway remodeling possibly by increasing HGF levels in asthmatic rats.
Angiotensin II ; analysis ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Asthma ; drug therapy ; metabolism ; pathology ; Bronchi ; chemistry ; drug effects ; pathology ; Hepatocyte Growth Factor ; analysis ; Immunohistochemistry ; Male ; Rats ; Rats, Sprague-Dawley ; Tetrazoles ; pharmacology ; therapeutic use ; Transforming Growth Factor beta1 ; analysis ; Valine ; analogs & derivatives ; pharmacology ; therapeutic use ; Valsartan
8.Angiogenesis related gene expression profiles of EA.hy926 cells induced by irbesartan: a possible novel therapeutic approach.
Cong MA ; Xue-chun LU ; Yun LUO ; Jian CAO ; Bo YANG ; Yan GAO ; Xian-feng LIU ; Li FAN
Chinese Medical Journal 2012;125(8):1369-1375
BACKGROUNDAngiogenesis occurs commonly in various physiological and pathological processes. Improving blood supply through promoting angiogenesis is a novel approach for treating ischemic diseases. Angiotensin II type 1 receptor blockers (ARBs) dominate the management of hypertension, but evidence of their role in angiogenesis is contradictory. Here we explored the angiogenic effects of ARBs through characterizing gene expression of the human umbilical vein endothelial cell line EA.hy926 exposed to irbesartan.
METHODSThe human umbilical vein endothelial cell line EA.hy926 was grown for 72 hours after treatment with different concentrations of irbesartan. The cell proliferative capacity was assessed by CCK8 assay at 24, 48 and 72 hours. Gene expression levels in EA.hy926 cells responding to irbesartan were measured under optimal proliferation conditions by microarray analysis using Affymetrix U133 plus 2.0. The differential expression of genes involved in angiogenesis was identified through cluster analysis of the resulting microarray data. Quantitative RT-PCR and Western blotting analyses were used to validate differential gene expression related to the angiogenesis process.
RESULTSIn the 10(-4), 10(-5), 10(-6) mol/L treatment groups, cell proliferation studies revealed significantly increased proliferation in EA.hy926 cells after 24 hours of irbesartan treatment. However, after 48 and 72 hours of treatment with different concentrations of irbesartan, there was no significant difference in cell proliferation observed in any treatment group. We selected the group stimulated with irbersartan at a concentration of 10(-6) mol/L for microarray experiments. Statistical analysis of the microarray data resulted in the identification of 56 gene transcripts whose expression patterns were significantly correlated, negatively or positively, with irbesartan treatment. Cluster analysis showed that these genes were involved in angiogenesis, extracellular stimulus, binding reactions and skeletal system morphogenesis. Of these 56 genes we identified seven genes (VEGF, KDR, PTGS2, PLXND1, ROBO4, LMO2, and COL5A1) involved in the angiogenesis process. qRT-PCR analysis of these genes confirmed the microarray results. Protein expression of three VEGF pathway genes (VEGF, KDR, and PTGS2) was further confirmed by Western blotting.
CONCLUSIONSOur study showed that irbesartan may induce angiogenic effects in vascular endothelial cells. It suggested that the mechanism of angiogenic effects of ARBs might be attributed to the signaling cascade from angiotensin receptors in the VEGF pathway. It also provided evidence indicating that ARBs could be used as a novel therapeutic approach to treat chronic ischemic heart disease as well as anti-hypertensive agents.
Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Antihypertensive Agents ; pharmacology ; Biphenyl Compounds ; pharmacology ; therapeutic use ; Cell Proliferation ; drug effects ; Cells, Cultured ; Endothelial Cells ; drug effects ; metabolism ; Gene Expression Profiling ; Humans ; Myocardial Ischemia ; drug therapy ; Neovascularization, Physiologic ; drug effects ; Tetrazoles ; pharmacology ; therapeutic use
9.Effects of valsartan on sarcoplasmic reticulum calcium adenosine triphosphatase, protein kinase A and protein phosphatase 1 alpha in a rabbit model of heart failure.
Fu-Zheng QU ; Zhi-Hua LIU ; Bin JIANG
Chinese Journal of Cardiology 2008;36(9):790-793
OBJECTIVETo investigate the effects of valsartan on expressions of myocardial sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2), protein kinase A (PKA) and protein phosphatase 1 alpha (PP1alpha) in a rabbit model of heart failure.
METHODSRabbits were divided into sham-operated group, heart failure group (volume overload by aortic valve destruction induced aortic insufficiency plus pressure overload induced by abdominal aortic banding) and heart failure plus valsartan (20 mgxkg(-1)xd(-1), n = 6 each). Seven weeks later, echocardiography examination was performed and SERCA2, PKA, PP1alpha protein and mRNA expressions were detected by Western blot and RT-PCR.
RESULTSCompared with the with sham operated rabbits, LVMI and LVEDP in heart failure rabbits were significantly increased while left ventricular shorten fraction (LVFS) and ejection fraction (EF) were significantly decreased (all P < 0.05), these changes could be significantly attenuated by valsartan treatment (all P < 0.05). SERCA2, PKA expressions at protein and mRNA levels were significantly downregulated and PP1alpha expressions significantly upregulated in heart failure rabbits than sham operated rabbits (all P < 0.05) and these changes could be significantly attenuated by valsartan (all P < 0.05).
CONCLUSIONValsartan improved cardiac function in volume and pressure overload induced heart failure rabbits possibly by upregulating expressions of myocardial SERCA2, PKA and downregulating expression of myocardial PP1alpha.
Animals ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; Female ; Heart Failure ; drug therapy ; metabolism ; Male ; Protein Phosphatase 1 ; metabolism ; Rabbits ; Sarcoplasmic Reticulum ; drug effects ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Tetrazoles ; pharmacology ; therapeutic use ; Valine ; analogs & derivatives ; pharmacology ; therapeutic use ; Valsartan
10.Role of valsartan on myocardial Calpain I, calcineurin and Ca/calmodulin-dependent protein kinase IIδ expression of renovascular hypertensive rats.
Jin-ya LU ; Jian-hua ZHU ; Xiao-tong QIN ; Xiao-hong YU ; Hong-zhuan SHENG
Chinese Journal of Cardiology 2012;40(6):511-515
OBJECTIVETo determine the protein expression of Calpain I, mRNA and protein expressions and activity of calcineurin, and the alternative splicing of Ca/calmodulin-dependent protein kinase II (CaMKII) δ in the hypertrophic heart, and to investigate the effect of angiotensin II type 1 receptor blocker valsartan (Val) on cardiac hypertrophy and the level of Calpain I, calcineurin and CaMKIIδ in renovascular hypertensive rats model.
METHODSRats were randomly divided into sham-operated control (n=8), hypertension (n=8) and hypertension plus Val (n=8, 30 mg×kg(-1)×(-1)). The renovascular hypertension was induced by two kidney-one clip methods in rats. The ratio of left ventricular weight to body weight was measured, the mRNA expression of calcineurin and alternative splicing of CaMKIIδ were determined by RT-PCR, the protein expression of Calpain I and calcineurin were measured by Western blot and the activity of calcineurin activity was assayed by a specialized kit.
RESULTSEight weeks after procedure, hypertension rats developed significantly cardiac hypertrophy, and the protein expression of Calpain I, mRNA and protein expression and the activity of calcineurin were significantly increased compared sham-operated control rats (all P<0.01), the mRNA expression of CaMKIIδA and B increased, CaMKIIδC mRNA decreased (P<0.01). Treatment with valsartan effectively attenuated cardiac hypertrophy and reversed hypertension induced changes on myocardial Calpain I, calcineurin and CaMKIIδ.
CONCLUSIONValsartan attenuates cardiac hypertrophy in renovascular hypertensive rats, possibly through inhibiting Calpain I, calcineurin and CaMKIIδ signaling pathways.
Animals ; Calcineurin ; metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; metabolism ; Calpain ; metabolism ; Hypertension, Renovascular ; drug therapy ; metabolism ; pathology ; Male ; Myocardium ; metabolism ; pathology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Tetrazoles ; pharmacology ; therapeutic use ; Valine ; analogs & derivatives ; pharmacology ; therapeutic use ; Valsartan