ramipril

Diabetic nephropathy (DN), a microvascular complication of diabetes, has emerged as an important health problem worldwide. There is strong evidence to suggest that oxidative stress, inflammation, and fibrosis play a pivotal role in the progression of DN. Apigenin has been shown to possess antioxidant, anti-inflammatory, anti-apoptotic, anti-fibrotic, as well as anti-diabetic properties. Hence, we evaluated whether apigenin halts the development and progression of DN in streptozotocin (STZ)-induced diabetic rats. Male albino Wistar rats were divided into control, diabetic-control, apigenin treatment groups (5-20 mg/kg p.o. respectively), apigenin per se (20 mg/kg p.o.) and ramipril treatment group (2 mg/kg p.o.). A single injection of STZ (55 mg/kg i.p) was administered to all the groups, except control and per se groups, to induce type 1 diabetes mellitus. Rats with fasting blood glucose > 250mg/dl were included in the study and randomized to different groups. Thereafter, the pro...

The aim of this study was to compare the mechanical and intrinsic effects of an angiotensin converting enzyme inhibitor, vs a beta-blocker, on brachial arterial compliance. In a double blind study, 34 essential hypertensive patients were treated for 3 months with either ramipril 2.5-5.0 mg daily (n = 17, age 57 +/- 7 y, 11 males) or atenolol 50-100 mg daily (n = 17, age 53 +/- 8 y, 11 males). Blood pressure (BP), brachial artery diameter (D), brachial-radial pulse wave velocity (PWV) and effective compliance (Ceff), were measured before and at the end of the study. Isobaric evaluation (Ciso) was performed in the entire population studied at an average mean BP of 110 mmHg. Ramipril significantly reduced BP from 155 +/- 16/94 +/- 6 mmHg to 140 +/- 15/85 +/- 7 mmHg (p < 0.001) without affecting heart rate (HR; 74 +/- 10 vs. 75 +/- 12 bpm). In addition, it significantly improved both PWV (18%; p < 0.001) and arterial compliance (45%; p < 0.001), from which 35% was related to a ...

The aim of this nation-wide cohort study was to assess the association of using an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) therapy on the prognosis of hypertensive patients with chronic kidney disease (CKD).We used Cox's proportional hazard regression model to estimate hazard ratios (HRs) for the risk of end-stage renal disease (ESRD), all-cause mortality, cardiovascular mortality, and first hospitalization for cardiovascular disease (CVD) for losartan and ramipril versus conventional antihypertensive agents.In total, 136,266 hypertensive patients with CKD in Taiwan were followed up from 2001 to 2008. In an average follow-up of 5.9 years, 7364 (5.40%) patients reached ESRD, 4165 (3.06%) patients died, and 6163 (4.52%) patients had their first hospitalization for CVD. Use of losartan or ramipril was associated with a lower risk of the endpoints compared with the conventional group. In the losartan group, the risks of ESRD, all- and ...

We hypothesized that peroxisome proliferator-activated receptors (PPARs) might be involved in a complex protective action of ACE inhibitors (ACEi) in anthracyclines-induced cardiomyopathy. For purpose of study, we compared effects of ramipril on cardiac dysfunction, cardiac failure markers and PPAR isoforms in moderate and severe chronic daunorubicin-induced cardiomyopathy. Male Wistar rats were administered with a single intravenous injection of daunorubicin: 5mg/kg (moderate cardiomyopathy), or 15mg/kg (severe cardiomyopathy) or co-administered with daunorubicin and ramipril (1mg/kg/d, orally) or vehicle for 8 weeks. Left ventricular function was measured invasively under anesthesia. Cardiac mRNA levels of heart failure markers (ANP, Myh6, Myh7, Myh7b) and PPARs (alpha, beta/delta and gama) were measured by qRT-PCR. Protein expression of NADPH subunit (gp91phox) was measured by Western blot. Moderate cardiomyopathy exhibited only minor cardiac dysfunction what was corrected by ramipril. In severe cardiomyopathy, hemodynamic dysfunction remained unaltered upon ramipril although it decreased the significantly up-regulated cardiac ANP mRNA expression. Simultaneously, while high-dose daunorubicin significantly decreased PPARbeta/delta and PPARgama mRNA, ramipril normalized these abnormalities. Similarly, ramipril reduced altered levels of oxidative stress-related gp91phox. On the other hand, ramipril was unable to correct both the significantly decreased relative abundance of Myh6 and increased Myh7 mRNA levels, respectively. In conclusion, ramipril had a protective effect on cardiac function exclusively in moderate chronic daunorubicin-induced cardiomyopathy. Although it normalized abnormal PPARs expression and exerted also additional protective effects also in severe cardiomyopathy, it was insufficient to influence impaired cardiac function probably because of a shift in myosin heavy chain isoform content.

Baseline BP and LVEF were similar, 131/76 mm Hg and 58%, in all treatment groups. After four years, LVM index increased by 3.98 ± 2.08 g/m 2 in the placebo and by 4.16 ± 1.86 g/m 2 in the ramipril 2.5 mg/day groups and decreased by 2.02 ± 2.25 g/m 2 in the ramipril 10 mg/day ...

Quality by design (QbD) is an essential part of the modern approach to pharmaceutical quality. This study was conducted in the framework of a QbD project involving ramipril tablets. Preliminary work included identification of the critical quality attributes (CQAs) and critical process parameters (CPPs) based on the quality target product profiles (QTPPs) using the historical data and risk assessment method failure mode and effect analysis (FMEA). Compendial and in-house specifications were selected as QTPPs for ramipril tablets. CPPs that affected the product and process were used to establish an experimental design. The results thus obtained can be used to facilitate definition of the design space using tools such as design of experiments (DoE), the response surface method (RSM) and artificial neural networks (ANNs). The project was aimed at discovering hidden knowledge associated with the manufacture of ramipril tablets using a range of artificial intelligence-based software, with the intention of establishing a multi-dimensional design space that ensures consistent product quality. At the end of the study, a design space was developed based on the study data and specifications, and a new formulation was optimized. On the basis of this formulation, a new laboratory batch formulation was prepared and tested. It was confirmed that the explored formulation was within the design space.

Damping is the conversion of mechanical energy of a structure into thermal energy, and it is related to the material viscous behavior. To evaluate the role of damping in the common carotid artery (CCA) wall in human hypertension and the possible improvement of angiotensin-converting enzyme (ACE) inhibition, we used noninvasive CCA pressure (tonometry) and diameter (B-mode echography) waveforms in normotensive subjects (NT group; n=12) and in hypertensive patients (HT group; n=22) single-blind randomized into HT–placebo (n=10) or HT-treated (ramipril, 5 to 10 mg/d during 3 months; n=12). Vascular smooth muscle (VSM) null tonus condition was achieved from in vitro pressure and diameter waveforms (Konigsberg microtransducer and sonomicrometry) measured in explanted human CCA (n=14). Arterial wall dynamics was described by viscous (η), inertial ( M ), and compliance ( C ) parameters, mean circumferential wall stress, viscous energy dissipation ( W D ), peak strain energy ( W St ), dampi...

We studied in coronary conductance and resistance arteries the coronary vasodilator effects of the angiotensin-converting enzyme inhibitor ramiprilat and the contribution of nitric oxide, bradykinin, and prostaglandins to this vasodilation. In seven anesthetized dogs, a Doppler guidewire was placed in the circumflex coronary artery to measure coronary flow velocity, and an ultrasound imaging catheter was introduced over the Doppler wire to measure coronary cross-sectional area. Drugs were infused directly into the left main coronary artery to minimize systemic effects. Ramiprilat increased both epicardial cross-sectional area and coronary blood flow velocity, resulting in an increase in absolute coronary blood flow. Pretreatment with N omega-nitro-L-arginine methyl ester (100 micromol/L intracoronary) to block nitric oxide synthase attenuated ramiprilat-induced increase in epicardial coronary cross-sectional area (P<.05) but not in coronary flow velocity or coronary blood flow. In contrast, pretreatment with the selective bradykinin antagonist HOE 140 (10 micromol/L) attenuated ramiprilat-induced increase in flow velocity (P<.025) and coronary blood flow (P<.05) but not epicardial coronary cross-sectional area. Pretreatment with indomethacin (5 mg/kg body wt IV) did not alter ramiprilat-induced increase in epicardial cross-sectional area, nor did it significantly influence coronary blood flow. Other than decreasing angiotensin II production, acute ramiprilat-induced vasodilation in canine coronary conductance arteries is mediated in part by nitric oxide. Ramiprilat-induced vasodilation in resistance arteries is in part mediated by the action of bradykinin.

Studies have challenged the appropriateness of accepted blood pressure targets. We hypothesised that different levels of low blood pressure are associated with benefit for some, but harm for other outcomes. In this analysis, we assessed the previously reported outcome data from high-risk patients aged 55 years or older with a history of cardiovascular disease, 70% of whom had hypertension, from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination, with a median follow-up of 56 months. Detailed descriptions of randomisation and intervention have already been reported. We analysed the associations between mean blood pressure achieved on treatment; prerandomisation baseline blood pressure; or time-updated blood pressure (last on treatment value before an event) on the composite outcome of cardiovascular death, myocardial infarction, stroke, and hospital admission for heart failure; the components of the composite outcome; and all-cause death. Ana...

Methods and Results—Beginning 2 days after transmural anteroapical MI, 62 sheep were treated with 1 of 5 treatment regimens: no therapy (control, n=12), standard-dose ACEI (sACEI; ramipril 10 mg/d, n=14), high-dose ACEI (hACEI; ramipril 20 mg/d, n=8), AT 1 blockade (losartan ...

Objectives To explore participants' opinions and preferences on tailored written medicines information. Methods Forty-five participants were recruited to eight focus groups, run concurrently in Australia (23 participants in four groups) and the UK (22 participants in four groups). Participants were provided with exemplar leaflets for a cardiovascular medicine based on the angiotensin-converting enzyme (ACE) inhibitor ramipril, which was tailored for a man aged 55 with hypertension. Reference to other indications of the medicine, children's doses, pregnancy and breast-feeding information were removed. A topic guide directed the discussion and explored preferences and opinions on tailored leaflets. Focus group discussions were recorded, transcribed verbatim and content analysed using adapted cross-case study analysis. Key findings Participants welcomed the concept of tailored information, desiring shorter and more relevant information. Information tailored to their condition o...

The renin-angiotensin system is involved in the progression of chronic renal disease of both diabetic and nondiabetic origin. The angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have been demonstrated to reduce urinary protein excretion and attenuate the development of renal injury. This prospective, randomized, 12-month study assessed the effects of ramipril (N = 23) vs. valsartan (N = 22) vs. combination of ramipril and valsartan (N = 26) on proteinuria, renal function and metabolic profile in 71 patients with nondiabetic proteinuria with normal or slightly impaired renal function. Monotherapy with ramipril or valsartan and combination of these two drugs significantly reduced proteinuria, serum creatinine, cholesterol and triglycerides as well as systolic and diastolic arterial blood pressure. There was no significant difference among three study groups according to reduction of arterial blood pressure, serum cholesterol and triglycerides. At one year...

The effect of intensified blood pressure (BP) control with a reduction of the diastolic BP to < or = 85 mm Hg on renal function and urinary albumin excretion (UAE) was studied in 28 men with primary hypertension (aged 62 to 72 years) treated for 13 +/- 5 years with beta-blockade, diuretics, or hydralazine. They were compared with 25 normotensive (NT) men of similar age. At baseline (BL), glomerular filtration rate (GFR), renal plasma flow (RPF) (clearance of inulin and para-aminohippurate), and the UAE were studied. Thereafter, all antihypertensive drugs except beta-blockers were withdrawn and either felodipine (5 to 20 mg; n = 13) or ramipril (2.5 to 10 mg; n = 15) was added in a double blind, randomized fashion. Hydrochlorothiazide was added if necessary. The investigations were repeated after 6 weeks and 1 year of double-blind treatment. At BL, the BP and the renal vascular resistance (RVR) were significantly higher and GFR and RPF were significantly lower in both hypertensive...