OBJECTIVETo investigate the effect of fosinopril (Fos) on regulating klotho gene expression and elucidate the mechanism of Fos regulating the Angiotensin II (AngII) -induced down-expression of klotho gene.

METHODSCulture cells, NRK-52E, were incubated with media either AngII or Fos or both of all. Experimental groups incubated with Fos (10(-5) mol/L) were divided according to variant points of time for 0 (control), 3, 6, 12, 24 h. Different concentration of Fos was selected to incubated with culture cells for 0 (control), 10(-9) 10(-8), 10(-7), 10(-6), 10(-5) mol/L at the optimal time point (24 h). Five groups, which were A: control; B: AngII (10(-7) mol/L); C: Fos(10(-5) mol/L); D: AngII (10(-7) mol/L) + Fos(10(-5) mol/L) and E: Cells pretreated with Fos(10(-5) mol/L)12 h incubated with AngII (10(-7) mol/L) were divided to observe the effect of Fos on expression of klotho induced by AngII. RT-PCR and immunohistochemistry (IHC) were applied to evaluate the klotho mRNA and protein expression, respectively.

RESULTSFos up-regulated klotho mRNA in time-dependent manner, and independent of dose-dependent manner; AngII obviously decreased the levels of kloltho mRNA and protein expression in NRK-52E as compared to the control (P < 0.05), the down-regulating effect was reversed by incubating both with AngII and Fos (P < 0.05), and Fos could inhibit the down-regulated expression of klotho gene induced by Ang II in NRK-52E.

CONCLUSIONFosinopril up-regulates klotho mRNA in time-dependent manner, and inhibits the down-regulated expression of klotho gene induced by Ang II.

Angiotensin II ; pharmacology ; Animals ; Cells, Cultured ; Down-Regulation ; Epithelial Cells ; drug effects ; metabolism ; Fosinopril ; pharmacology ; Gene Expression ; drug effects ; Glucuronidase ; genetics ; metabolism ; Kidney Tubules ; cytology ; drug effects ; metabolism ; RNA, Messenger ; genetics ; Rats

In the present study, the correlated activities of adjacent ganglion cells of transient subtype in response to full-field white light stimulation were investigated in the chicken retina. Pharmacological studies and cross-correlation analysis demonstrated that application of the GABA(A) receptor antagonist bicuculline (BIC) significantly down-regulated the correlation strength while increasing the firing activities. Meanwhile, application of the GABA(A) receptor agonist muscimol (MUS) potentiated the correlated activities while decreasing the firing rates. However, application of the GABA(C) receptor antagonist (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) did not have a consistent influence on either the firing rates or the correlation strength. These results suggest that in the chicken retina, correlated activities among neighborhood transient ganglion cells can be increased while firing activities are reduced with the activation of GABA(A) receptors. The GABA(A)-receptor-mediated inhibitory pathway may be critical for improving the efficiency of visual information transmission.
Action Potentials ; Animals ; Bicuculline ; pharmacology ; GABA-A Receptor Antagonists ; pharmacology ; Mice ; Muscimol ; pharmacology ; Phosphinic Acids ; pharmacology ; Pyridines ; pharmacology ; Receptors, GABA-A ; metabolism ; Retina ; physiology ; Retinal Ganglion Cells ; physiology ; gamma-Aminobutyric Acid

Adolescent ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Blood Pressure ; drug effects ; Child ; Child, Preschool ; Female ; Fosinopril ; pharmacology ; therapeutic use ; Humans ; Male ; Nephritis ; drug therapy ; Proteinuria ; drug therapy ; Purpura, Schoenlein-Henoch ; complications

OBJECTIVE: To determine the relation between plasma tissue factor (TF) and serum angiotensin II(AngII) and the effect of different dosages of fosinopril on chronic heart failure(CHF). METHODS: Thirty healthy controls and 35 CHF patients were recruited to observe AngII,TF, left ventricular ejection fractions(LVEF) and left ventricular end-systolic volume index (LVESVI) at baseline and 10 weeks after the treatment. The 35 patients were randomly assigned into 2 groups: A routine dosage fosinopril group received 10 mg once daily and a middle dosage group received 10 mg twice a day for 10 weeks. RESULTS: Compared with the healthy controls, AngII,TF,and LVESVI significantly increased (P<0.01) and LVEF significantly decreased (P<0.01) in CHF patients. The TF was positively correlated with AngII(r=0.2491, P<0.01) in the patients. After the 10-week treatment with different dosages of fosinopril, AngII,TF,and LVESVI obviously decreased(P<0.05 or P<0.01) and LVEF significantly increased in the 2 groups (P<0.05 or P<0.01). The middle dosage group changed more than the routine dosage group (P<0.01). CONCLUSION TF is positively correlated with AngII in CHF patients. Fosinopril can greatly improve cardiac function and antagonize prethrobotic state,and the therapeutic effect improves with the dosage increase.
Aged ; Angiotensin II ; blood ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; Chronic Disease ; Female ; Fosinopril ; administration & dosage ; Heart Failure ; blood ; drug therapy ; Humans ; Male ; Middle Aged ; Thromboplastin ; metabolism

OBJECTIVE: To determine the mechanism of Toll-like receptor 4(TLR4) in hypertensive renal injury and the protective effect of fosinopril(Fos) and losartan(Los). METHODS: NRK-52E was incubated into 5 groups: NRK-52E (normal control), NRK-52E+AngII, NRK-52E+AngII+Fos(10(-5) mmol/L),and NRK-52E+AngII+Los(10(-5) mmol/L), NRK-52E +AngII+Fos(10(-5) mmol/L)+Los(10(-5) mmol/L). TLR4-specific RNAi plasmids were stably transfected into NRK-52E. After 24 h, TLR4, IL-6, and TNF-alpha mRNAs were examined by reverse transcription-polymerase chain reaction(RT-PCR). TLR4 proteins were detected by Western blot, NF-kappaB nuclear translocations were tested by immunocytochemistry,and IL-6 and TNF-alpha supernatant levels were tested by enzyme linked immuno-sorbent assay(ELISA). RESULTS: TLR4, NF-kappaB, IL-6,and TNF-alpha were highly expressed in AngII induced NRK-52E(P<0.01). In NRK-52E that was stably transfected TLR4-special RNAi plamids, TLR4 protein and mRNA expression were obviously inhibited(P<0.05). After stimulation by AngII, the TLR4, IL-6, TNF-alpha levels in the stabe transfection group were increased compared with the normal group(P<0.05). Fos or/and Los down-regulated TLR4, IL-6, and TNF-alpha expressions(P<0.05), but no cooperation was observed. CONCLUSION TLR4 may lead to inflammatory reaction in hypertensive renal injury. Fos or/and Los can decrease the expressions of TLR4 and correlate inflammatory factors, which may be part of the renal protective mechanism.
Animals ; Cell Line ; Epithelial Cells ; immunology ; metabolism ; Fosinopril ; pharmacology ; Hypertension ; complications ; Kidney Diseases ; prevention & control ; Kidney Tubules ; cytology ; metabolism ; Losartan ; pharmacology ; RNA Interference ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Toll-Like Receptor 4 ; biosynthesis ; genetics

OBJECTIVETo observe the effects of fosinopril (FOS) on proliferation and secretion of extracellular matrix of rat glomerular mesangial cell induced by LPS.

METHODSIn vitro culture method for glomerular mesangial cells (GMC) of rat was established and passages 3 - 10 of the cells were used in the experiment after identification. The experiment included the following 5 groups: control group (Ctrl), LPS group (LPS), high, medium and low dose FOS groups (FOS1, FOS2 and FOS3 groups, respectively). GMC proliferation was detected by methyl thiazolyl tetrazolium (MTT) incorporation method at 24 and 48 h; the changes of laminin (LN), fibronectin (FN) and ColIV protein secretion was detected by the enzyme-linked immunosorbent assay (ELISA). The changes of LNbeta(2) mRNA expression was detected by semi-quantitative real-time RT-PCR.

RESULTS(1) LPS could induce the mesangial cell proliferation, FOS inhibited this effect of proliferation induced by LPS. (2) Mesangial cells could secrete some extracellular matrix (ECM) protein in normal culture medium, mesangial cell secreted ECM protein was significantly higher in LPS group than that in Ctrl group (P < 0.01), but significantly lower in all FOS groups than that in LPS group (P < 0.01). (3) Mesangial cell could express LNbeta(2) mRNA in normal culture medium, LNbeta(2) mRNA expression was significantly higher in LPS group than that in Ctrl group at all time points, but was significantly lower in FOS group than that in LPS group.

CONCLUSIONSLPS could induce increased secretion of the ECM, including LN, FN, ColIV; FOS could inhibit the secretion of ECM in GMC in a dose-dependent manner at mRNA and protein levels.

Animals ; Cell Proliferation ; Cells, Cultured ; Extracellular Matrix Proteins ; secretion ; Fosinopril ; pharmacology ; Gene Expression Regulation ; Lipopolysaccharides ; Mesangial Cells ; drug effects ; metabolism ; Rats

OBJECTIVE: To compare the nephrotoxicity of high- and low-osmolar contrast media (HOCM and LOCM), and to determine the protective role of fosinopril or telmisartan and its possible mechanism. METHODS: Forty eight healthy SD rats were randomly divided into 6 groups: a normal control group, a glycerol control group, a low-osmolar contrast media (LOCM) group, a high-osmolar contrast media (HOCM) group, a fosinopril group, and a telmisartan group. Glycerine for inducing kidney damage was given to all rats except the normal control group. Twenty-four hours after the injection of glycerine, the mixed fosinopril suspension (10mg/kg) or telmisartan (5mg/kg) was poured into the stomach in the preventive group. Serum creatinine (SCr) and plasma angiotensin II (AngII) levels were detected by an automatical biochemical analyzer and radioimmunoassay; caspase-3 activity and claudin-1 expression of the renal tissue were detected by fluorometric method and immunohistochemical method. The renal injury was assessed by hematoxylin and eosin (HE) staining and terminal deoxynucleotide mediated nick and labeling (TUNEL) staining, respectively. RESULTS: In diatrizoate-injected rats, SCr and AngII levels were increased (P<0.05). Expression of claudin-1 protein and caspase-3 activity in the renal tissue was upregulated. The histologic changes and percentage of apoptotic cells were milder in the LOCM rats than those in the HOCM rats. In the group pretreated with fosinopril or telmisartan, no increase in the levels of SCr and AngII was discovered. The expression of claudin-1 protein and caspase-3 activity was significantly lower than that in the HOCM group. The renal injuries induced by diatrizoate were alleviated. CONCLUSION Both HOCM and LOCM could cause cellular apoptosis in the kidney.LOCM was less toxic to rat kidney than HOCM. Nephrotoxicity induced by HOCM might be related to caspase-3, claudin-1 and AngII. Fosinopril or telmisartan may protect the renal tissue from nephrotoxicity induced by diatrizoate.
Angiotensin II ; blood ; Animals ; Apoptosis ; drug effects ; Benzimidazoles ; pharmacology ; Benzoates ; pharmacology ; Caspase 3 ; metabolism ; Claudin-1 ; metabolism ; Contrast Media ; administration & dosage ; toxicity ; Creatinine ; blood ; Female ; Fosinopril ; pharmacology ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Telmisartan

OBJECTIVETo investigate the effect of fosinopril and metoprolol on metalloproteinases 9 (MMP9) expression of human umbilical vein endothelial cells (HUVECs) stimulated by oscillatory flow.

METHODSHUVECs were exposed to steady laminar flow or oscillatory flow, laminar flow or oscillatory flow plus various concentrations (1 x 10(-7) mol/L, 1 x 10(-5) mol/L) of fosinopril and metoprolol for 4 and 24 hours. MMP9 mRNA and protein expressions of HUVECs were determined by RT-PCR and Western blot, respectively.

RESULTSMMP9 expression at mRNA and protein levels were significantly increased in HUVECs exposed to oscillatory flow than that to laminar flow and these could be down-regulated by coincubation with fosinopril (1 x 10(-7) mol/L, 1 x 10(-5) mol/L, P < 0.01, P < 0.05, respectively) but not by co-incubation with metoprolol.

CONCLUSIONFosinopril can attenuate the increased MMP9 expression at mRNA and protein levels of HUVECs exposed to oscillatory flow.

Cells, Cultured ; Endothelial Cells ; drug effects ; metabolism ; Endothelium, Vascular ; Fosinopril ; pharmacology ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; Metoprolol ; pharmacology ; RNA, Messenger ; metabolism ; Stress, Mechanical ; Umbilical Veins ; cytology

OBJECTIVETo investigate the effect of garlicin in treating carotid artery atherosclerotic plaque (CAAP) in patients with primary hypertension and coronary heart disease (PHT-CHD).

METHODSSeventy-nine patients with PHT-CHD were randomly divided into the treated group (39 patients) treated with garlicin and fosinopril and the control group (40 patients) treated with fosinopril alone. The change of CAAP was evaluated by high frequency ultrasonic examination every six months, and the changes of intercellular adhesion molecule-1 (ICAM-1) and high sensitive C-reactive protein (hs-CRP) were measured by ELISA, with the observation proceeding for 52 weeks totally.

RESULTSBy the end of the experiment, the number of complex plaques, Crouse integrals, intima-media thickness, serum ICAM-1 and hs-CRP were significantly lower in the treated group than those in the control group with significant difference (P < 0.05).

CONCLUSIONGarlicin could stabilize CAAP to a certain extent and shows a definite vascular protective effect in patients with PHT-CHD.

Aged ; Allyl Compounds ; administration & dosage ; Antihypertensive Agents ; administration & dosage ; Blood Pressure ; drug effects ; C-Reactive Protein ; metabolism ; Carotid Artery Diseases ; complications ; diagnostic imaging ; drug therapy ; Coronary Artery Disease ; complications ; drug therapy ; Disulfides ; administration & dosage ; Female ; Fosinopril ; administration & dosage ; Humans ; Hypertension ; complications ; drug therapy ; Intercellular Adhesion Molecule-1 ; blood ; Male ; Middle Aged ; Ultrasonography

OBJECTIVETo evaluate the effects of fosinopril on myocardial no-reflow in a mini-swine model of acute myocardial infarction and reperfusion.

METHODSTwenty-four mini-swines were randomized into 3 study groups: 8 in control group, 8 in fosinopril-treated group (1 mg.kg(-1).d(-1)) and 8 in sham-operated group. Animals in the former two groups were subjected to 3 hours of coronary occlusion followed by 60 minutes of reperfusion. Data on haemodynamics and coronary blood flow volume (CBV) were collected, and the area of no-reflow was evaluated with both myocardial contrast echocardiography (MCE) in vivo and pathological means. Necrosis area was measured with triphenyltetrazolium chloride (TTC) staining.

RESULTS(1) In the control group, systolic and diastolic blood pressure (SBP and DBP), left ventricular systolic pressure (LVSP), maximal rate of increase and decrease in left ventricular pressure (+/- dp/dt(max)) and cardiac output (CO) significantly declined (P < 0.05-0.01), while left ventricular end-diastolic pressure (LVEDP) and pulmonary capillary wedge pressure (PCWP) significantly increased at the end of 3 hours occlusion of left anterior descending artery (both P < 0.01). Compared with those at the end of 3 hours of occlusion, +/- dp/dt(max) further significantly declined (P < 0.05) at 60 minutes of reperfusion. In the fosinopril group, the changes of SBP and DBP, LVSP, +/- dp/dt(max), CO, LVEDP and PCWP were similar as those in the control group after 3 hours of acute myocardial infarction. In contrast, LVSP, +/- dp/dt(max), CO, LVEDP and PCWP recovered significantly at 60 minutes of reperfusion. (2) In the control group, the coronary ligation area was similar on both MCE in vivo and pathological evaluation, and the area of no-reflow was similarly as high as 78.5% and 82.3%, respectively, with final necrosis area reaching 99% of ligation area. In the fosinopril group, there was no significant difference in ligation area on both MCE and pathological evaluations between the fosinopril and control groups, although the area of no-reflow on both methods was significantly decreased to 24.5% and 25.2%, respectively, (P < 0.01) with final necrosis area of pathological evaluation being also significantly decreased to 88.9% of LA (P < 0.05). (3) In the control group, CBV was significantly declined to 45.8% and 50.6% from at baseline, immediately after release of occlusion (3 hours) and at 60 minutes of reperfusion (P < 0.01). In the fosinopril group, CBV was also significantly declined immediately after release of occlusion (3 hours), and at 60 minutes of reperfusion (P < 0.05), but significantly increased to 69.1% and 72.1% from at baseline, that were significantly greater than those in the control group (both P < 0.01).

CONCLUSIONFosinopril is effective in preventing myocardial no-reflow, improving left ventricular function, and reducing infarct area during acute myocardial infarction and reperfusion in mini-swine.

Animals ; Blood Flow Velocity ; drug effects ; Disease Models, Animal ; Female ; Fosinopril ; pharmacology ; therapeutic use ; Male ; Myocardial Infarction ; drug therapy ; Myocardial Reperfusion ; methods ; Myocardial Reperfusion Injury ; prevention & control ; Swine ; Swine, Miniature