Development and validation of UV- spectrophotometer method for determination of fosinopril sodium in raw material and tablets

The effective Angiotensine Converting Enzyme inhibitors Fosinopril is widely used in the treatment of hypertension and congestive Heart Failure. Specific sensitive and rapid UV method have been developed for assaying Fosinopril sodium in raw material and in tablets. The assay was performed using wave length at 220 nm, methanol and water [4/1] V/V as solution. The method was validated according to the parameters [Linearity, Accuracy, Precision, Specificity, Raptness, Limit of detection, Limit of quantification], all validation parameters were within the acceptance range

Fosinopril up-regulates and ameliorates the Ang II induced down-expression of klotho gene in NRK-52E / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Culture 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.</p><p><b>RESULTS</b>Fos 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.</p><p><b>CONCLUSION</b>Fosinopril up-regulates klotho mRNA in time-dependent manner, and inhibits the down-regulated expression of klotho gene induced by Ang II.</p>

Protective effect of fosinopril sodium pretreatment combined with ischemic postconditioning on rat heart underwent myocardial ischemia/reperfusion injury / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of fosinopril sodium pre-treatment combined with ischemic postconditioning on rat serum and myocardial oxidative stress and proinflammatory cytokines post ischemia/reperfusion.</p><p><b>METHODS</b>Sixty Sprague-Dawley rats were randomly divided into sham group (n = 15), ischemia/reperfusion group (30 minutes in situ occlusion of the left anterior descending artery followed by 1 hour reperfusion, n = 15), IPoC group (30 minutes occlusion of the left anterior descending artery followed by 3 cycles of 10 seconds of reperfusion/10 seconds of ischemia before 1 hour reperfusion, n = 15) and fosinopril sodium group [pretreated with fosinopril sodium (0.9 mg×kg(-1)×d(-1) for 14 days) followed by IPoC protocol at 2 h after the last gavage, n = 15]. The arterial blood and heart samples were extracted after 1 hour reperfusion. Serum CK-MB and cTnT levels were detected by colorimetric method, myocardial infarction size was measured by nitrotetrazolium blue chloride staining, SOD content was examined by colorimetric method, MDA content was detected using thiobarbituric acid method, serum levels of Interleukin-1α (IL-1α), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were examined by radioimmunoassay, IL-1α, IL-6 and TNF-α levels of myocardial tissue were detected by ELISA.</p><p><b>RESULTS</b>Compared with I/R group, myocardial enzymes and infarction size were significantly decreased (P < 0.05, P < 0.01), serum SOD content was increased and MDA content was decreased (all P < 0.01), serum and myocardial levels of IL-1α, IL-6 and TNF-α were significantly reduced (P < 0.05, P < 0.05, P < 0.01) in IPoC group. Compared with IPoC group, fosinopril sodium pretreatment further reduced infarction size and myocardial enzyme CK-MB (P < 0.05), increased SOD content (P < 0.05) while reduced serum IL-6 and myocardial tissue TNF-α (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Pretreatment with fosinopril sodium enhanced the protective effect of IPoC on rat myocardium underwent I/R injury, possibly by reducing oxidative stress and early inflammatory reaction.</p>

Plasma tissue factor and serum angiotensin II and the therapeutic effect of different dosages of fosinopril on chronic heart failure / 中南大学学报(医学版)

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.

Colorimetric determination of ramipril, enalapril maleate and fosinopril in their pharmaceutical formulations

Two new spectrophotometric methods were developed for the determination of three angiotensin-converting enzyme inhibitors, namely, ramipril, enalapril maleate and fosinopril. The first method was based on the oxidation of the three drugs by Fe[III] in presence of 1.10-phenanthroline, the formed tris-[Fe-o-phen]complex in acetate buffer and optimum pH was measured at [lambda][max] 510 nm with linear relationship over concentration range from 6-50 micro gml[-1] and molar absorptivity 1.2x10[4] 1 mol[-1]cm[-1] for ramipril and enalapril maleate and 1.8x10[4] 1 mol[-1]cm[-1] for fosinopril. The second method was based on measuring the formed tris -[Fe-bipyridyl]complex in the same condition at [lambda][max] 540 nm with linear relationship in concentration range from 10-54 micro gml[-1] and molar absorptivity of 1.0x10[4] 1 mol[-1]cm[-1] for ramipril, 1.6x10[4] 1 mol[-1]cm[-1] for and enalapril maleate and 1.57x10 [4] mol[-1]cm[-1] for fosinopril. The two methods hold their accuracy and precision well when applied to the determination of the studied drugs in their dosage forms

Antidepressant activity of fosinopril, ramipril and losartan, but not of lisinopril in depressive paradigms of albino rats and mice.

Fosinopril, ramipril and losartan significantly decreased the duration (sec) of immobility in forced swim test and were comparable to amitriptyline. The duration of immobility were significantly decreased in fosinopril, ramipril and losartan in the tail suspension test and were comparable to amitriptyline. Only losartan significantly increased the rearing number of entries, time spent (sec) in open arm and in light area in comparison to control animals. Fosinopril and ramipril and not lisinopril showed significant antidepressant activity while losartan showed a significant antidepressant and anxiolytic activity. Present findings suggest that these drugs could be better antihypertensives in hypertensive patients with comorbidity like depression or anxiety.

Effects of fosinopril and losartan on the expression of Toll- like receptor 4 in renal tubular epithelia cells / 中南大学学报(医学版)

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.

Effects of fosinopril on proliferation and secretion of extracellular matrix of rat glomerular mesangial cell / 中华儿科杂志

<p><b>OBJECTIVE</b>To observe the effects of fosinopril (FOS) on proliferation and secretion of extracellular matrix of rat glomerular mesangial cell induced by LPS.</p><p><b>METHODS</b>In 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.</p><p><b>RESULTS</b>(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.</p><p><b>CONCLUSIONS</b>LPS 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.</p>

Nephrotoxicity of high- and low-osmolar contrast media: Protective role of fosinopril or telmisartan in a rat model / 中南大学学报(医学版)

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.

Clinical study on effect of Garlicin in stabilizing the carotid artery atherosclerotic plaque in patients with primary hypertension and coronary artery disease / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of garlicin in treating carotid artery atherosclerotic plaque (CAAP) in patients with primary hypertension and coronary heart disease (PHT-CHD).</p><p><b>METHODS</b>Seventy-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.</p><p><b>RESULTS</b>By 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).</p><p><b>CONCLUSION</b>Garlicin could stabilize CAAP to a certain extent and shows a definite vascular protective effect in patients with PHT-CHD.</p>

Fosinopril but not metoprolol attenuated the increased matrix metallo-proteinases 9 expression at mRNA and protein levels of human umbilical vein endothelial cells exposed to oscillatory flow / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of fosinopril and metoprolol on metalloproteinases 9 (MMP9) expression of human umbilical vein endothelial cells (HUVECs) stimulated by oscillatory flow.</p><p><b>METHODS</b>HUVECs 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.</p><p><b>RESULTS</b>MMP9 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.</p><p><b>CONCLUSION</b>Fosinopril can attenuate the increased MMP9 expression at mRNA and protein levels of HUVECs exposed to oscillatory flow.</p>

Effects of pravastatin, fosinopril and their combination on myocardium TNF-alpha expression and ventricular remodeling after myocardial infarction in rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of pravastatin, fosinopril and their combination on ventricular remodeling, cardiac function, tumor necrosis factor-alpha (TNF-alpha) mRNA expression, and matrix metalloproteinases (MMPs) activities after myocardial infarction (MI) in rats.</p><p><b>METHODS</b>Acute myocardial infarction (AMI) was established by ligation of the anterior descending coronary artery in male Sprague-Dawly (SD) rats. Twenty-four hours after the procedure, the 48 surviving rats were grouped randomly as AMI control, fosinopril (10 mg.kg(-1).d(-1)), pravastatin (20 mg.kg(-1).d(-1)) and a combined use of the 2 drugs. Sham-operated group (n = 8) was taken randomly as non-infarction control. Six weeks after treatment with the drugs by gastric gavage, heart function and left ventricular remodeling were assessed. Left ventricular weight (LVW)/body weight (BW) ratio was determined. The relative expression of myocardium TNF-alpha mRNA was assessed by reverse transcription-polymerase chain reaction. Left ventricular myocardium MMPs activities were assessed by Zymography.</p><p><b>RESULTS</b>There were no significant differences among the four AMI groups in infarction size (P > 0.05). In comparison with the AMI group, left ventricular end-diastolic pressure, left ventricular end-diastolic diameter, LVW/BW all decreased significantly (P < 0.05 - 0.01); while dp/dtmax, dp/dtmin, fractional shortening (FS) and ejection fraction (EF) increased significantly in all three drug-treated groups (P < 0.05 - 0.01); increments of FS, LVEF and dp/dtmax were more evident in the combination group than either the fosinopril or pravastatin group (P < 0.05). The levels of TNF-alpha mRNA in AMI rats treated with fosinopril, pravastatin and their combination reduced 29%, 26% and 33%, respectively (P < 0.01); MMP-2 activity reduced 25%, 30% and 35%, respectively (P < 0.01); MMP-9 activity reduced 20%, 18% and 24%, respectively (P < 0.01). There were no significant differences in other variables among the 3 treatment groups (P > 0.05).</p><p><b>CONCLUSION</b>Pravastatin, fosinopril and their combination showed favorable effects on left ventricular remodeling after AMI in rats and demonstrated improved cardiac function. The combined treatment group yielded better results in the context of improving left ventricular systolic function. These effects could be relevant to the attenuation of increased MMP-2 and MMP-9 activities and left ventricular expression of TNF-alpha.</p>

Beneficial effects of fosinopril on myocardial no-reflow in a mini-swine model of acute myocardial infarction and reperfusion / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of fosinopril on myocardial no-reflow in a mini-swine model of acute myocardial infarction and reperfusion.</p><p><b>METHODS</b>Twenty-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.</p><p><b>RESULTS</b>(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).</p><p><b>CONCLUSION</b>Fosinopril is effective in preventing myocardial no-reflow, improving left ventricular function, and reducing infarct area during acute myocardial infarction and reperfusion in mini-swine.</p>

possible reno- and vascufoprotective of drugs that inhibit the renin angiotensin system in diabetic rats

Aim: The renin angiotensin system [RAS] plays an important role in the development of diabetic renovascular pathology characteristic of diabetic nephropathy [DN]. Through inhibition of RAS by different mechanisms, angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin II type 1 receptor blockers [ARBs] could slow the progression of diabetic renovascular disease. Thus, the present study was undertaken to test the hypothesis that a combination of an ACEI [fosinopril] and an ARB [candesartan] could exert additive reno- and vasculoprotective effects in uninephrectomized [UNE], streptozotocin [STZ] -induced diabetic rats. Material and Fifty male albino rats weighing 150-200 g were used in the present study. Rats were divided into five groups [each of ten rats]; ten rats of them were taken as normal sham-operated group. The remaining forty rats were subjected to left unilateral nephrectomy and then three weeks later, diabetes was induced by a single intravenous injection of STZ. The UNE STZ - diabetic rats were further subdivided into: control rats that were given no additional treatment but insulin s.c., UNE STZ -diabetic rats treated with fosinopril in addition to insulin for 16 weeks, UNE STZ - diabetic rats treated with candesartan in addition to insulin for 16 weeks and the fifth group was UNE STZ -diabetic rats treated with a combination of fosinopril and candesartan in addition to insulin for 16 weeks. UNE STZ - diabetic rats exhibited the characteristic features of diabetic renal disease including increased BP, plasma creatinine [PCr], urinary albumin excretion [UAE], kidney weight [KW], BG and glycosylated hemoglobin [HbAIc] together with decreased urinary creatinine [UCr] and creatinine clearance [CrCI]. Furthermore, control rats showed significant elevations in plasma transforming growth factor-beta 1 [TGF-D 1] and in renal malondialdehyde [MDA] associated with significant reduction in renal reduced glutathione [GSH]. Edothalial dysfunction [ED] of renal arteries isolated from STZ-diabetic rats, evidenced by a significant decrease in percentage of maximal relaxation in response to acetylcholine [ACH], has been also demonstrated. Oral administration of fosinopril or candesartan for 16 weeks in UNE STZ diabetic rats produced significant decreases in KW,BP, PCr,UAE, plasma TGED1 and renal MDA concentration together with significant increase in UCr, CrC 1 and renal GSH concentration. Vasculoprotective effect of fosinopril and candesartan has been also found, evidenced by a significant increase in the percentage of maximal relaxation in response to Ach in renal arteries isolated from UNR STZ-diabetic rats treated with fosinopril or candesartan Treatment of UNE diabetic rats with a combination of an ACEI [Fosinopril] and an ARB [candesartan] improved most of the estimated biochemical parameters as well as BP more significantly than either drug alone, but the combination of both drugs did not result in a significant difference in the percentage of maximal relaxation in response to Ach in renal arteries compared to either drug given alone. Conclusions: the results of the present study demonstrated that ACEIs and ARBs have a comparable degree of reno- and vasculoprotection in UNE STZ- induced diabetic rats Moreover, the present study demonstrated an additive renoprotective effect of combination therapy with ACEIs and ARBs over monotherapy with either class alone

Protection of organic trauma in sinoaortic-denervated rats treated with fosinopril / 药学学报

<p><b>AIM</b>To study the importance of blood pressure variability in organ protection for long-term treatment with fosinopril in-sinoaortic-denervated (SAD) rats.</p><p><b>METHODS</b>Fosinopril (15 mg.kg-1.d-1) was given in rat chow for 16 weeks after SAD surgery. Blood pressure variability (BPV) was recorded during 24 h in conscious state. Histopathological changes were evaluated with light microscope and computer-assisted image analysis.</p><p><b>RESULTS</b>Long-term treatment with fosinopril significantly decreased BPV in SAD rats. The thickness of the left ventricular wall, collagen fraction of the left ventricle and glomerulosclerosis score were all positively related to BPV in untreated and fosinopril-treated SAD rats. Fosinopril markedly prevented the damages of target organs in SAD rats.</p><p><b>CONCLUSION</b>Long-term treatment with fosinopril showed obvious organ protection in SAD rats. The decrease in BPV may significantly contribute to organ protection.</p>

Effect of amlodipine, fosinopril and atenolol on glucose metabolism and microalbuminuria in STZ diabetic rats

This study compares the effect of a calcium channel blocker [amlodipine], an ACE inhibitor [fosinopril] and a B 1-blocker [atenolol] on blood glucose level, plasma insulin level, insulin sensitivity and 24 hours urinary albumin excretion in groups of rats made diabetic by a single intraperitoneal injection of streptozotocin [STZ] [60 mg/kg]. Five groups of rats were used in this work. The first group [control non-diabetic rats] was normoglycemic with blood glucose level 116.8 +/- 9.4 mg/dl and 24 hour[H] urinary albumin 8.2 +/- 1.2 mg/24 H urine. The other four groups were made diabetic by a single dose of STZ. The second group [control non-treated diabetic rats] exhibited hyperglycemia 8 weeks after induction of diabetes with blood glucose level 354 +/- 32.6 mg/dl, plasma insulin level 10.1 +/- 0.8 mIU/ml and 24 H urinary albumin 42.6 +/- 3.2 mg/24 H wine. Results of this study revealed that amlodipine oral administration in a dose of 5 mg/kg for 8 weeks in the third group of STZ diabetic rats induced a significant reduction of blood glucose level [234 +/- 18.6 versus 354 +/- 32.6 in control diabetic rats, P< 0.05] and plasma insulin level [8.2 +/- 06 mIU/ml versus 10.1 +/- 0.8 mIU/ml in control diabetic rats, P<0.05]. Amlodipine also caused significant reduction in 24 H urinary albumin [18.2 +/- 1.2 mg versus 42.6 +/- 3.2 mg in control diabetic rats, P<0.05] and significant improvement in sensitivity to intraperitoneal bolus dose of insulin where it caused a significant reduction in blood glucose level at 0.5 H,1 H and 6 H after insulin compared to control diabetic rats, P<0.05. The results of this study also revealed that administration of fosinopril in a dose of 5 mg/kg/day oral to the fourth group of STZ diabetic rats for 8 weeks induced a significant reduction in blood glucose level plasma insulin level, and 24 H urinary albumin excretion compared to control non-treated diabetic rats. Fosinopril, also produced a significant improvement in insulin sensitivity at 0.5 H, 1 H and 6 H after insulin injection compared to control non-treated diabetic rats. In contrast, atenolol given orally in a dose of 10 mg/kg/day for 8 weeks to fifth group of diabetic rats did not induce a significant change in blood glucose level, plasma insulin level and 24 H urinary Albumin and even reduced insulin sensitivity compared to control non-treated diabetic rats. It could be concluded from these results that both amlodipine and fosinopril are better antihypertensives than atenolol in diabetic patients as they improved glucose tolerance and albuminuria in STZ diabetic rats

Effects of fosinopril and valsartan on expressions of ICAM-1 and NO in human umbilical vein endothelial cells / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the effects of fosinopril and valsartan on the expression of intercellular adhesion molecule-1 (ICAM-1) and nitric oxide (NO) induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells.</p><p><b>METHODS</b>The levels of NO, ICAM-1, and nitric oxide synthase (NOS) were determined using the nitrate reductase method, ELISA, immunohistochemical and image analyses.</p><p><b>RESULTS</b>The ox-LDL can significantly increase the expression of ICAM-1 and inhibit the expression of NO and NOS in a dose-dependent manner. Fosinopril and valsartan can significantly inhibit these roles of ox-LDL. The roles of fosinopril and valsartan were not significantly different.</p><p><b>CONCLUSION</b>Fosinopril and valsartan inhibit oxidized LDL-induced expression of ICAM-1 and increase the expression of NO in human umbilical vein endothelial cells, which is one of the mechanisms of antiatherosclerosis.</p>

The effect and mechanism of forsinopril on ventricular hypertrophy of SHR and left ventricular pressure overloading rat / 华中科技大学学报（医学）（英德文版）

The effects and mechanism of long-term angiotensin converting enzyme inhibitor (ACEI) Forsinopril on left ventricular hypertrophy of spontaneous hypertension rat (SHR) and left ventricular pressure overloading rat were studied. The left ventricular index (left ventricle weight/body weight) was used to evaluate left ventricular hypertrophy and the in situ hybridization to investigate the TGF-beta 1 gene expression in left ventricle. The results showed that Forsinopril significantly decreased the left ventricular index of both SHR and left ventricle pressure overloading rat. Forsinopril reduced the integral photic density of TGF-beta 1 gene statement from 2.836 +/- 0.314 to 1.91 +/- 0.217 (P < 0.01, n = 8) of SHR rat and from 3.071 +/- 0.456 to 2.376 +/- 0.379 (P < 0.01, n = 8) of left ventricular pressure overloading rat respectively. It was concluded that Forsinopril could prevent the occurrence of left ventricular hypertrophy and reduce the TGF-beta 1 gene expression in left ventricle of both SHR and left ventricular pressure overloading rat significantly.

Apoptosis, myocardial fibrosis and angiotensin II in the left ventricle of hypertensive rats treated with fosinopril or losartan / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the different effects of an angiotensin II type 1 (AT(1)) receptor antagonist, losartan, and an angiotensin converting enzyme (ACE) inhibitor, fosinopril, on cardiomyocyte apoptosis, myocardial fibrosis, and angiotensin II (Ang II) in the left ventricle of spontaneously hypertensive rats (SHRs).</p><p><b>METHODS</b>SHRs of 16-week-old were randomly divided into 3 groups: SHR-L (treated with losartan, 30 mg.kg(-1) x d(-1)), SHR-F (treated with fosinopril, 10 mg x kg(-1) x d(-1)), and SHR-C (treated with placebo). Each group consisted of 10 rats. Five rats, randomly selected from each group, were killed at the 8th and 16th week after treatment. Cardiomyocyte apoptosis, collagen volume fraction (CVF), perivascular collagen area (PVCA) and Ang II concentrations of plasma and myocardium were examined.</p><p><b>RESULTS</b>Compared with the controls at the 8th and 16th week, systolic blood pressures were similarly decreased in both treatment groups. Left ventricular weight and left ventricular mass indexes were significantly lower in both treatment groups. However, the latter parameter at the 16th week was reduced to a less extent in the fosinopril group than that in the losartan group. Compared with the controls, cardiomycyte apoptotic index was significantly reduced at the 8th week only in the fosinopril group, and at the 16th week in both treatment groups. The index of the fosinopril group was lower than that of the losartan group at the latter endpoint examined. Compared with the controls, the left ventricular collagen volume fraction and perivascular collagen area at the 8th and 16th weeks were significantly reduced in the SHRs treated with either fosinopril or losartan. However, the collagen volume fraction at the latter endpoint in the fosinopril group was lower than that in the losartan group. Compared with the controls at endpoints, plasma and myocardium Ang II levels were significantly increased in the losartan group. However, plasma Ang II concentrations were not altered, and myocardium Ang II concentrations at the 8th and 16th weeks were significantly reduced in the fosinopril group.</p><p><b>CONCLUSIONS</b>Both losartan and fosinopril could effectively inhibit cardiomyocyte apoptosis and myocardial fibrosis and reverse heart hypertrophy. Fosinopril may be more effective in these cardioprotective effects, suggesting that the effects of both drugs are related to the inhibition of myocardium renin-angiotension-aldsterone system.</p>