Monopril

Monopril is a medication used in the treatment of hypertension and heart failure. It controls the blood pressure levels, but it does not actually cure either disease, just keeps them under control. It belongs to a class of drugs known as ACE inhibitors and it works by preventing the chemical angiotensin I from converting into a different substance which increases salt and water retention in the body. This action makes the blood vessels relax so blood can flow smoother and thus pressure is not elevated. It is important to note that besides its most prominent use in heart failure and hypertension, Monopril is also an excellent remedy for diabetic neuropathy. Monopril works alone or in combination with other drugs and is one of the preferred choices for blood pressure control.

Int J Clin Pract. 2005 Mar;59(3):306-10.
Effects of amlodipine and fosinopril on heart rate variability and left ventricular mass in mild-to-moderate essential hypertension.
Bilge AK, Atilgan D, Tukek T, Ozcan M, Ozben B, Koylan N, Meric M.
Department of Cardiology, Istanbul University, 34390 Capa, Istanbul, Turkey. ahmetkayabilge@hotmail.com

The differences between long-acting dihydropyridines and angiotensin-converting enzyme inhibitors with regard to their long-term effects on 24-h heart rate variability (HRV) and left ventricular (LV) mass are less clear in mild-to-moderate essential hypertension. We studied the long-term effects of amlodipine and fosinopril on 24-h HRV and LV mass in mild-to-moderate essential hypertension. In this study, 27 patients with never treated mild-to-moderate essential hypertension were randomised to receive either amlodipine or fosinopril once daily as monotherapy. At baseline and at the end of the third and sixth months, each of the patients underwent 24-h HRV and ambulatory systolic (SBP) and diastolic (DBP) blood pressure analysis. LV mass index was calculated from echocardiographic examination at baseline and at the end of the sixth month. In amlodipine group (n = 14), 24-h SBP/DBP (mmHg) decreased from 144 +/- 8/94 +/- 4 to 128 +/- 6/83 +/- 3 at the end of the third month and to 125 +/- 5/81 +/- 2 at the end of the sixth month (p < 0.0001). In fosinopril group (n = 13), the respective changes were 143 +/- 9/97 +/- 7, 132 +/- 6/87 +/- 5 and 127 +/- 6/82 +/- 3 (p < 0.0001). At the end of the sixth month, LV mass index (g/m(2)) decreased from 122 +/- 26 to 105 +/- 21 in amlodipine group (p < 0.0001) and from 118 +/- 23 to 101 +/- 14 in fosinopril group (p < 0.0001). There were no significant changes in HRV parameters in both the groups. It was concluded that both drugs caused significant decrease in SBP and DBP, and LV mass in patients with mild-to-moderate essential hypertension did not have significant long-term effects of either amlodipine or fosinopril on 24-h HRV parameters reflecting sympathetic or parasympathetic activity in these patients.

Nephrol Dial Transplant. 2005 May;20(5):892-901. Epub 2005 Mar 8.
Expression and activation of STAT3 in chronic proliferative immune complex glomerulonephritis and the effect of fosinopril.
Zhang W, Chen X, Shi S, Wei R, Wang J, Yamanaka N, Hong Q.
Department of Nephrology, General Hospital of PLA, Beijing 28 Fuxing Road, 100853, P.R. China. xmchen@public.bta.net.cn.

BACKGROUND: Signal transducers and activators of transcription (STATs) are cytoplasmic proteins that are activated in response to stimulation from various cytokines. Among these, STAT3 is an important member that has been implicated in the inflammatory proliferation of cells. We hypothesized that STAT3 may be activated in kidneys of rats having modified chronic immune complex glomerulonephritis, and that angiotensin-converting enzyme (ACE) inhibition with fosinopril may prevent the activation of STAT3 and subsequent upregulation of tissue inhibitor of metalloproteinase-1 (TIMP-1), which are effects that may explain the therapeutic effects of fosinopril on nephritis. METHODS: Fifty-one Wistar rats were randomly divided into three groups that included a control group, a model group and a fosinopril group. Bovine serum albumin (BSA) nephritis was induced by subcutaneous immunization and daily intraperitoneal (i.p.) administration of BSA. To accentuate the nephritis, we performed uni-nephrectomy and gave 100 microg of lipopolysaccharide (LPS) as an i.p. injection. Macrophage infiltration (ED-1) was assessed with immunohistochemistry. The expression and activation of STAT3 and the expression of TIMP-1, one of the STAT3 downstream genes, were observed in renal tissues of rats by means of immunohistochemistry, electrophoretic mobility shift assay (EMSA), western blot and northern blot. The relationships between STAT3 phosphorylation, 24 h urinary protein excretion and TIMP-1 expression were also analysed. RESULTS: Northern blot showed that the mRNA expression of both STAT3 and TIMP-1 was significantly increased in kidneys from the model group, but significantly decreased in the fosinopril group (P<0.05). Western blot analysis revealed similar increases in the expression of STAT3, phospho-STAT3 (p-STAT3) and TIMP-1 in the model group. Analysis of immunohistochemistry showed that STAT3 and p-STAT3 were expressed in very few cells of normal rats, that expression was strong in model rats and that this increased expression was attenuated in the fosinopril group (P<0.05). The expression of p-STAT3 in glomeruli was positively correlated with 24 h proteinuria as well as with glomerular TIMP-1 expression. Double staining showed that some ED-1-positive cells also contained p-STAT3-positive staining. CONCLUSIONS: The present study showed that STAT3 is expressed and activated in kidneys of rats with modified immune complex glomerulonephritis. These rats also had increased ED-1-positive cells, with some cells showing simultaneous expression of p-STAT3 and ED-1, which may contribute to glomerular inflammatory proliferation and extracellular matrix accumulation. Finally, fosinopril downregulated STAT3 activation and ED-1 influx, which are effects that may attenuate renal damage in this model.

Stroke. 2005 Mar;36(3):649-53. Epub 2005 Feb 03.
Effects of fosinopril and pravastatin on carotid intima-media thickness in subjects with increased albuminuria.
Asselbergs FW, van Roon AM, Hillege HL, de Jong PE, Gans RO, Smit AJ, van Gilst WH; PREVEND IT Investigators.
Department of Clinical Pharmacology, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands. f.w.asselbergs@thorax.azg.nl

BACKGROUND AND PURPOSE: Elevated urinary albumin excretion (UAE) is associated with an increased carotid intima-media thickness (IMT). Because angiotensin-converting enzyme inhibitors as well as statins have been shown to lower UAE and the progression of IMT, we assessed the effects of fosinopril and pravastatin on carotid IMT in subjects with an increased UAE (15 to 300 mg/24 h). METHODS: IMT was measured at the posterior wall of the left common carotid artery using radio-frequency signal analysis obtained by M-mode ultrasonography. 642 subjects were double-blind randomized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo and were available for intention-to-treat analysis. RESULTS: Mean age was 51+/-11 years, 65% were male, the median UAE was 22.5 (15.5 to 40.8) mg/24 h, and the mean IMT at baseline was 0.77+/-0.18 mm. The overall progression rate of IMT in 4 years was 0.037+/-0.006 mm. No significant difference in IMT progression was found between fosinopril, pravastatin, or matching placebo. IMT after 4 years was predicted by IMT at baseline, age, gender, pulse pressure, and low-density lipoprotein cholesterol levels. Furthermore, a higher incidence of clinical events was observed in subjects with an IMT >1 mm after a mean follow-up of 46+/-7 months (hazard ratio, 3.13; 95% confidence interval, 1.59 to 6.16; P=0.001). CONCLUSIONS: In subjects with an increased UAE, treatment with fosinopril and pravastatin showed no significant effect on carotid IMT. Furthermore, an IMT <1 mm at baseline is an important indicator for event-free survival.

Pharmacol Res. 2004 Aug;50(2):131-6.
Studies on the glycemic and lipidemic effect of monopril and losartan in normal and diabetic rats.
el-Batran SA, el-Shenawy SM, Nofal SM, Abdel-Salam OM, Arbid MS.
Department of Pharmacology, National Research Center, Doki, Cairo, Egypt. sehamelbatran@yahoo.com
The effects of the angiotensin-converting enzyme (ACE) inhibitor monopril and the angiotensin II receptor blocker losartan on serum glucose, protein levels and some serum lipid components were compared in normal and diabetic rats receiving oral antidiabetic drugs 'repaglinide or gliclazide'. The two antihypertensive agents, when administered concurrently with oral hypoglycemic agents 'repaglinide or gliclazide' in normal and diabetic rats exerted a significant hypoglycemic effect. Serum protein levels were mainly unaffected by the two antihypertensive drugs. Monopril and losartan exhibit a hypolipidemic effect in normal and diabetic rats when administered in combination with oral hypoglycemic agents 'gliclazide or repaglinide'. Monopril or losartan when used alone exerted insignificant effect in high density lipoprotein (HDL) in normal rats, while in combination with gliclazide or repaglinide caused a significant increase in HDL in normal rats. Concomitantly, monopril or losartan, when administered alone or in combination with repaglinide or gliclazide in diabetic rats exerted a significant increase in serum HDL. On the other hand, all the investigated drugs showed a significant decrease in serum low density lipoprotein (LDL) in normal and diabetic rats. Copyright 2004 Elsevier Ltd.

J Vasc Res. 2004 Mar-Apr;41(2):148-56. Epub 2004 Mar 03.
Role of Angiotensin-converting enzyme and neutral endopeptidase in flow-dependent remodeling.
Korshunov VA, Massett MP, Carey RM, Berk BC.
Center for Cardiovascular Research and Department of Medicine, University of Rochester, Rochester, NY 14642, USA.
Omapatrilat inhibits neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). We compared the effects of omapatrilat (40 mg/kg/day, p.o.) to fosinopril (40 mg/kg/day, p.o.) on flow-induced vascular remodeling in New Zealand genetically hypertensive (GH) rats. Both drugs equally reduced blood pressure (BP) initially, but systolic BP and pulse pressure were reduced more by omapatrilat after 1 week. Carotid remodeling was induced by partial ligation of the left common carotid artery (LCA). There was little remodeling in untreated GH rats - measured as outer diameter to body weight (OD/BW vs. before ligation): 97 +/- 1% of initial LCA (low flow) and 107 +/- 3% of initial right common carotid artery (RCA, high flow). In contrast, OD/BW increased to 118 +/- 5% (p < 0.05) of initial RCA after omapatrilat versus 108 +/- 2% (p = 0.96) after fosinopril. The major change was increased RCA lumen area which was significantly larger in omapatrilat-treated animals (127% vs. control) than fosinopril-treated animals (103% vs. control). The increase in outward remodeling after omapatrilat treatment correlated weakly with vascular cGMP levels and decreased systolic BP. The results suggest that dual inhibition of NEP/ACE may have greater effects than ACE inhibition alone on vessel remodeling in hypertension. Copyright 2004 S. Karger AG, Basel

Clin Exp Hypertens. 2004 Jan;26(1):69-80.
Cardiorenal protective effects of vasopeptidase inhibition with omapatrilat in hypertensive transgenic (mREN-2)27 rats.
Mifsud SA, Burrell LM, Kubota E, Jaworski K, Cooper ME, Wilkinson-Berka JL.
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.
Vasopeptidase inhibitors simultaneously inhibit both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The aim of this study was to determine the cardiorenal effects of the vasopeptidase inhibitor omapatrilat in the transgenic m(Ren-2)27 rat which exhibits fulminant hypertension and severe organ pathology. At 6 weeks of age, male Ren-2 rats were randomized to receive no treatment (N = 10), the ACE inhibitor fosinopril 10 mg/kg/day (N = 10), or omapatrilat 10 mg/kg/day (N = 10) or 40 mg/kg/day (N = 10) by daily gavage for 24 weeks. Various cardiorenal functional and structural parameters were assessed. Compared to controls, all treatment groups reduced hypertension in control Ren-2 rats, with both doses of omapatrilat reducing systolic blood pressure significantly more than fosinopril (control, 178 +/- 3 mmHg; fosinopril 10 mg/kg/day, 130 +/- 4 mmHg; omapatrilat 10 mg/kg/day, 110 +/- 3 mmHg; omapatrilat 40 mg/kg/day, 91 +/- 3 mmHg). Omapatrilat dose-dependently reduced cardiac hypertrophy, caused a greater inhibition of renal ACE than fosinopril, and was the only treatment to inhibit renal NEP. Attenuation of albuminuria, glomerulosclerosis and cardiorenal fibrosis occurred to a similar degree with omapatrilat and fosinopril. Omapatrilat confers cardiorenal protection in the hypertensive Ren-2 rat. Although inhibition of tissue NEP may contribute to the superior blood pressure reduction by omapatrilat, overall, the results are consistent with the central role that angiotensin II plays in renal and cardiac fibrosis in this model of hypertension.

Am J Hypertens. 2003 Nov;16(11 Pt 1):931-7.
Effect of dual angiotensin converting enzyme/neutral endopeptidase inhibition, angiotensin converting enzyme inhibition, or AT1 antagonism on coronary microvasculature in spontaneously hypertensive rats.
Pu Q, Larouche I, Schiffrin EL.
CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec, Canada.
Microvascular remodeling contributes to increased cardiovascular risk in hypertension. The dual angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) inhibitor omapatrilat improves small artery remodeling in hypertension. The aim of the present study was to compare effects of omapatrilat to the ACE inhibitor fosinopril and the AT(1) antagonist irbesartan on the coronary microvasculature in spontaneously hypertensive rats (SHR). Ten-week-old SHR were treated for 10 weeks with omapatrilat (20 or 40 mg/kg/d), irbesartan (50 mg/kg/d), or fosinopril (20 mg/kg/d). Arterioles and capillaries were identified in the myocardium by immunolabeling. After 10 weeks, systolic blood pressure (BP) was significantly reduced in treated versus untreated SHR (P <.01). Myocardial arteriolar density/mm(2) was higher (P <.05) in untreated SHR versus Wistar-Kyoto (WKY), and was reduced by omapatrilat (at both high and low doses) and by fosinopril (P <.01). Irbesartan decreased only subepicardial arteriolar density (P <.05). Myocardial capillary density/mm(2) was decreased in untreated SHR versus WKY (P <.01), associated with increase in cardiomyocyte cross-sectional area and cardiomyocyte-to-capillary ratio, and a decrease in myocyte density. Omapatrilat (at both high and low doses) resulted in increased capillary density, decreased myocyte hypertrophy and cardiomyocyte to capillary ratio, and increased myocyte density (P <.01). Fosinopril and irbesartan reduced myocyte hypertrophy of SHR, but had no effect on capillary density. Dual ACE/NEP inhibition was more effective than ACE inhibition or AT(1) antagonism in improving microvascular and cardiomyocyte remodeling in the hypertensive heart. This suggests a role for NEP inhibition added to blockade of the renin-angiotensin system that may explain the greater efficacy of omapatrilat.

Di Yi Jun Yi Da Xue Xue Bao. 2003 Sep;23(9):963-5.
Combination therapy with losartan and fosinopril for early diabetic nephropathy
Huang YH, Wang HT, Zhu QZ, Zhang H, Shen W, Wang Y.
Department of Nephrology, Guangzhou General Hospital of Guangzhou Command, Guangzhou 510010, China.
OBJECTIVE: To observe the effects of combined use of losartan and fosinopril in the treatment of early diabetic nephropathy. METHODS: Fifty-seven patients with diabetic nephropathy were divided equally into group A with treatment with losartan (50 mg) and fosinopril (10 mg) daily, group B with daily losartan treatment (50-100 mg), and group C with fosinopril treatment at the daily dose of 10-20 mg. After the 6-month medication, the patients underwent examinations for changes in the mean arterial blood pressure (MABP), serum creatinine (SCr), blood urea nitrogen (BUN) and 24-h urine protein excretion. RESULTS: Losartan or fosinopril used alone or in combination significantly lowered MABP, 24-h urine protein excretion, SCr and BUN in the patients ( P < 0.05 or P < 0.01). In spite of the absence of significant differences between the patient groups, combination use of the two drugs produced the most obvious reduction of the parameters measured. CONCLUSION: Combined use of losartan and fosinopril may decrease MABP, 24-h urine protein excretion, SCr and BUN to a greater extent than the use of losartan or fosinopril alone.


Kardiologiia. 2003;43(2):29-34.
Efficacy of combined use of fosinopril and propranolol in acute myocardial infarction
Agaev MM, Azizov VA.
Echocardiography, Doppler echocardiography and ECG mapping were used in 40 patients aged 30-70 years with first anterior Q-wave myocardial infarction (MI) for the study of effects of combination of fosinopril and propranolol (20 patients) in comparison with propranolol alone (20 patients) on hemodynamics and size of myocardial damage. The use of fosinopril and propranolol was associated with lowering of systolic and diastolic blood pressure without development of hypotension, reduction of sum, number of leads with, and amplitude of ST-segment elevations, and improvement of parameters of left ventricular function. In propranolol treated patients favorable changes of all these parameters were less pronounced. Inhospital clinical course of the disease was also better in patients treated with fosinopril and propranolol.

Fundam Clin Pharmacol. 2002 Oct;16(5):353-60.
FOSIDIAL: a randomised placebo controlled trial of the effects of fosinopril on cardiovascular morbidity and mortality in haemodialysis patients. Study design and patients' baseline characteristics.
Zannad F, Kessler M, Grunfeld JP, Thuilliez C; FOSInopril in DIALysis Investigators.
Hypertension and Preventive Cardiology Division, Department of Cardiovascular disease, and Centre d'Investigations Cliniques INSERM-CHU, Toul, France. cic@chu-nancy.fr
The prevalence of end stage renal disease (ESRD) is growing in western countries.
Patients with ESRD are more frequently elderly and diabetic and are exposed to very high cardiovascular morbidity and mortality. The main aim of the FOSIDIAL study is to assess the efficacy and safety of fosinopril, an angiotensin converting enzyme (ACE) inhibitor, in reducing the mortality and cardiovascular events in haemodialysis patients presenting with left ventricular hypertrophy. A total number of 397 patients are included in the study. They are aged 50-80 years (average 66.7 years) and have been undergoing haemodialysis for 4.8 years. All have left ventricular hypertrophy with cardiac mass index > 100 g/m2 in women and > 130 g/m2 in men, measured within 3 months prior to inclusion. Baseline cardiac mass index is 174 g/m2. After a 2 week placebo period, the patients are randomised into two groups receiving either fosinopril 5-20 mg/day, or a placebo for a duration of 24 months. The target dose is reached at the sixth, seventh or eighth week of treatment. Depending on tolerance, 300 patients reached the maximum recommended dose. Patients are subsequently assessed clinically every 3 months until the end of the study. The primary outcome is a composite endpoint of fatal and nonfatal major cardiovascular events. Secondary endpoints are individual cardiovascular events, event-free survival, overall mortality and all-cause hospitalisations. The trial began in October 1998. All patients were included by December 2000 and follow-up is ongoing. The last visit for the last patient is scheduled for 30 December 2002. We report here on the study design and the baseline characteristics of the study population.

An Med Interna. 2002 Nov;19(11):571-5.
Comparison of the antihypertensive activity of fosinopril and irbesartan
Angulo E, Robles NR, Grois J, Barquero A, Perez Miranda M.
Servicio de Medicina Interna, Centro de Salud Anexo I, Hospital Infanta Cristina, Badajoz.
OBJECTIVE: To compare the antihypertensive effect of two daily single dose drugs acting on the renin-angiotensin axis by two different ways. METHODS: Thirty patients were randomized to receive either irbesartan (150 mg once daily) (n = 15, mean age 65.2 +/- 8.7 years, 9 men and 6 women) or fosinopril (20 mg once daily) (n = 15, mean age 57.4 +/- 11.5 years, 4 men and 11 women, difference are not significant) during 12 weeks. When needed, hydroclorothiazide (12.5 mg) was added to treatment to improve hypotensive response. RESULTS: A reduction of SBP and DBP was observed in both treatment groups throughout the study. In order to obtain further BP reduction, hydrochlorothiazide was added to 6 patients with inadequate BP response at the 4th week (3 patients in the irbesartan group) and 8th week (2 patients in irbesartan group and 1 patient in fosinopril group). SBP was reduced in irbesartan group from 157.7 +/- 11.2 to 131.0 +/- 8.7 mmHg (12th week, p < 0.001). DBP decreases from 94.1 +/- 5.6 to 82.7 +/- 4.2 mmHg (p < 0.001). In fosinopril group SBP was reduced from 147.9 +/- 11.7 to 132.2 +/- 12.4 mmHg (p < 0.001) and DBP decreases from 92.3 +/- 6.3 to 84.0 +/- 5.4 mmHg (p < 0.001). Final between group differences in BP are not significant. Final BP reduction in irbesartan group (26.7 +/- 11.6 mmHg) was bigger than that obtained in fosinopril group (15.6 +/- 11.6 mmHg, p = 0.011). BP reduction was significant in fosinopril group from the first month (SBP 140.7 +/- 12.2, p = 0.021; DBP 87.2 +/- 6.2, p = 0.003). In irbesartan group BP reduction was not significant until the second month (SBP 135.5 +/- 10.4, p < 0.001; DBP 85.3 +/- 4.3, p < 0.001). CONCLUSIONS: Fosinopril and irbesartan seems to be equally effective to reduce DBP. Irbesartan might have higher effectiveness on systolic blood pressure. Irbesartan act more gradually than fosinopril and this may be useful to prevent from acute blood pressure falls.

Am J Hypertens. 2002 Dec;15(12):1042-9.
Effects of amlodipine fosinopril combination on microalbuminuria in hypertensive type 2 diabetic patients.
Fogari R, Preti P, Zoppi A, Rinaldi A, Corradi L, Pasotti C, Poletti L, Marasi G, Derosa G, Mugellini A, Voglini C, Lazzari P.
Department of Internal Medicine and Therapeutics, Clinica Medica IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy
BACKGROUND: The aim of this study is to compare the long-term effect of amlodipine and fosinopril in monotherapy or in combination on urinary albumin excretion (UAE) in hypertensive diabetic patients. METHODS: We selected 453 hypertensive patients with type 2 diabetes and microalbuminuria and randomized them to amlodipine (5 to 15 mg/day), fosinopril (10 to 30 mg/day), or amlodipine plus fosinopril (5/10 to 15/30 mg/day) for a 3-month titration period. The nonresponder patients or those complaining of side effects during the titration period were discontinued (n = 144); the remaining 309 patients were enrolled in the trial and treated with the same therapy for 4 years. Every 6 months, blood pressure (BP), heart rate (HR), UAE, creatinine clearance, and glycosylated hemoglobin (HbA1c) were evaluated. RESULTS: The combination therapy was more effective in reducing BP than either drug alone at any time of the study without affecting glucose homeostasis. All three treatments provided a significant decrease in UAE during the 48-month study period. However, this effect was more pronounced and became evident earlier with fosinopril than with amlodipine monotherapy (after 3 v 18 months of therapy). In addition, the combination therapy provided a greater antialbuminuric effect than the single drugs. This could be due to the greater antihypertensive effects, although other drug-specific effects cannot be excluded. The cardiovascular outcomes were similar in the amlodipine and in the fosinopril group, but they were lower in the combination group. CONCLUSIONS: These results strengthen the rationale to use a calcium-antagonist/angiotensin converting enzyme inhibitor combination in the treatment of hypertensive patients with type 2 diabetes.