ramipril and Inflammation

Topics: Angiotensin-Converting Enzyme Inhibitors; Arteriosclerosis; C-Reactive Protein; Cardiovascular Diseases; Humans; Inflammation; Myocardial Infarction; Prognosis; Ramipril; Risk Factors; Stroke

Hypertension, endothelial dysfunction, and inflammation are associated with increased cardiovascular mortality in end-stage kidney disease. We evaluated the effects of ACE (angiotensin-converting enzyme) inhibition on biomarkers of endothelial dysfunction and inflammation in hypertensive children with end-stage kidney disease on maintenance hemodialysis.. In a randomized, double-blind, placebo-controlled trial, 135 (72 males/63 females) children and adolescents (age 7-15 years) were randomly assigned to treatment with either 2.5 mg once daily ramipril (n=68) or placebo (n=67) for 16 weeks. Primary outcome were the serum concentrations of asymmetrical dimethylarginine, a marker of endothelial dysfunction and hs-CRP (high-sensitivity C-reactive protein), a marker of inflammation. Changes in IL-6 (interleukin-6), TNF-α (tumor necrosis factor-alpha), systolic (S), and diastolic (D) blood pressure were secondary outcomes. Change in potassium levels and incidence of hyperkalemia were among the safety parameters.. Ramipril, but not placebo, significantly reduced serum levels of asymmetrical dimethylarginine (-79.6%;. Ramipril improves biomarkers of endothelial dysfunction and inflammation in hypertensive children on maintenance hemodialysis in addition to its efficacious and safe potential to lower blood pressure.. URL: https://www.. gov; Unique identifier: NCT04582097.

Topics: Adolescent; Antihypertensive Agents; Biomarkers; Blood Pressure; C-Reactive Protein; Child; Double-Blind Method; Female; Humans; Hyperkalemia; Hypertension; Inflammation; Interleukin-6; Kidney Failure, Chronic; Male; Ramipril; Renal Dialysis; Tumor Necrosis Factor-alpha

Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We examined the contribution of the angiotensin-converting enzyme inhibitor ramipril and the alpha 1-adrenergic receptor blocker doxazosin on blood pressure and on markers of inflammation and hemostasis in 59 individuals with mild-to-moderate hypertension randomized to receive double-blind ramipril 10 mg od or doxazosin 8 mg od for 12 weeks. Inflammatory markers (interleukin-6, soluble interleukin-6 receptor, interleukin-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and C-reactive protein) and hemostasis (plasminogen activator inhibitor-1 activity, tissue plasminogen activator antigen, thrombin-antithrombin complex, and thrombin generation by calibrated automated thrombogram) were assessed. The treatment reduced blood pressure in both groups. Thrombin-antithrombin complex decreased by treatment, and this was dependent on a reduction in thrombin-antithrombin complex in the ramipril group alone. There were no changes in plasminogen activator inhibitor-1 activity, whereas tissue plasminogen activator antigen increased by ramipril and decreased by doxazosin. Only minor changes were observed in systemic inflammation by treatment. Treatment with ramipril seems to reduce thrombin generation beyond effects on reducing blood pressure. Drugs blocking the renin-angiotensin-aldosterone system may reduce atherothrombotic complications beyond their effects to reduce blood pressure.

Topics: Adrenergic alpha-1 Receptor Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biomarkers; Blood Pressure; Double-Blind Method; Doxazosin; Female; Hemostasis; Humans; Hypertension; Inflammation; Inflammation Mediators; Male; Middle Aged; Ramipril; Renin-Angiotensin System; Sweden; Time Factors; Treatment Outcome

Biomarkers of oxidative stress and inflammation predict cardiovascular events in maintenance hemodialysis patients. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) reduce cardiovascular mortality in the general population, but their benefit in maintenance hemodialysis patients is not fully explored. To test whether ACE inhibitors and ARBs differentially affect markers of oxidative stress, inflammation, and fibrinolysis during hemodialysis, we conducted a randomized, double-blind, placebo-controlled 3×3 crossover study. We randomly assigned 15 participants undergoing hemodialysis to placebo, ramipril (5 mg/d), and valsartan (160 mg/d) for 7 days, with a washout period of 3 weeks in between the treatments. On the morning of the seventh day of drug treatment, participants underwent serial blood sampling during hemodialysis. Neither ramipril nor valsartan affected BP during hemodialysis. Ramipril increased IL-1β concentrations (P=0.02) and decreased IL-10 concentrations (P=0.04) compared with placebo. Valsartan and ramipril both lowered IL-6 levels during dialysis (P<0.01 for each compared with placebo). Valsartan increased F(2)-isoprostane levels, and ramipril suggested a similar trend (P=0.09). Valsartan and ramipril both lowered D-dimer levels (P<0.01 for both), whereas only ramipril seemed to prevent a rise in vWf levels (P=0.04). In summary, during hemodialysis, valsartan induces a greater anti-inflammatory effect compared with ramipril, although ramipril seems to prevent dialysis-induced endothelial dysfunction as measured by levels of vWf. A prospective clinical trial is necessary to determine whether ACE inhibitors and ARBs also differ with respect to their effects on cardiovascular mortality in this population.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Coagulation; CD40 Ligand; Cross-Over Studies; Cytokines; Double-Blind Method; Female; Hemodynamics; Humans; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Ramipril; Renal Dialysis; Renin; Tetrazoles; Valine; Valsartan

The effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor blockade (ARB) on fibrinolysis and inflammation after cardiopulmonary bypass (CPB) are uncertain. This study tested the hypothesis that ACE inhibition enhances fibrinolysis and inflammation to a greater extent than ARB in patients undergoing CPB. One week to 5 days before surgery, patients were randomized to ramipril 5 mg/day, candesartan 16 mg/day, or placebo. ACE inhibition increased intraoperative bradykinin and tissue-type plasminogen activator (t-PA ) concentrations as compared to AR B. Both ACE inhibition and AR B decreased the need for plasma transfusion relative to placebo, but only ACE inhibition decreased the duration of hospital stay. Neither ACE inhibition nor AR B significantly affected concentrations of plasminogen activator inhibitor-1 (PAI -1), interleukin (IL )-6, IL -8, or IL -10. ACE inhibition enhanced intraoperative fibrinolysis without increasing the likelihood of red-cell transfusion. By contrast, neither ACE inhibition nor ARB affected the inflammatory response. ACE inhibitors and ARBs may be safely continued until the day of surgery.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biphenyl Compounds; Blood Transfusion; Bradykinin; Cardiopulmonary Bypass; Endpoint Determination; Female; Fibrinolysis; Hematocrit; Hospital Mortality; Humans; Inflammation; Interleukins; Length of Stay; Male; Middle Aged; Monitoring, Intraoperative; Perioperative Care; Postoperative Complications; Ramipril; Tetrazoles; Treatment Outcome

This study investigated the effects of pioglitazone (PIO), ramipril (RAM), or their combination (PIRA) on low-grade inflammation in nondiabetic hypertensive patients with increased cardiovascular risk.. Patients enrolled in this placebo-controlled, double-blind, randomized, parallel trial (72 male, 77 female, aged 60 ± 9 years, body mass index 30.4 ± 4.7 kg/m(2), duration of hypertension 9 ± 8 years) were treated with either 30/45 mg PIO (dose titration), 2.5/5 mg RAM, or their combination for 12 weeks. A reduction in high-sensitivity C-reactive protein was observed with PIO (-0.89 ± 1.98 mg/liter; -25%) and PIRA (-0.49 ± 2.11 mg/liter; -16%), while an increase was seen with RAM (0.58 ± 2.13 mg/liter; +20%, p < .05 vs PIO and PIRA). The 24-hour blood pressure profile showed a small increase with both monotherapies but a decrease with PIRA (p < .05 vs PIO). Improvements in biomarkers of chronic systemic inflammation and insulin resistance (IR) were observed in the PIO and PIRA arms only [PIO/RAM/PIRA: homeostasis model of assessment of IR: -0.78 ± 1.39 (-29%)/0.15 ± 1.03 (+5%)/ -1.44 ± 2.83 (-40%); adiponectin: 8.51 ± 5.91 (+104%)/ 0.09 ± 2.63 (+1%)/ 8.86 ± 6.37 mg/liter (+107%); matrix metallo-proteinase-9: -48 ± 127 (-12%)/-1 ± 224 (0%)/-60 ± 210 ng/ml (-13%), p < .05 for RAM vs PIO or PIRA in all cases].. Our 3-month study in nondiabetic hypertensive patients showed a decrease in biomarkers of IR and chronic systemic inflammation with the PIO monotherapy and the PIRA combination only, which may help to explain some findings in other cardiovascular outcome trials.

Topics: Adult; Aged; Antihypertensive Agents; Biomarkers; Blood Vessels; Cardiovascular Diseases; Diabetes Complications; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Inflammation; Male; Middle Aged; Pioglitazone; Placebos; Ramipril; Risk Factors; Severity of Illness Index; Thiazolidinediones; Up-Regulation

Plasma visfatin levels are elevated in diabetic nephropathy in parallel to the severity of proteinuria and glomerular filtration rate. The aim of this study was to find out whether the renin-angiotensin-aldosterone system (RAAS) blockage has any effect on the plasma visfatin levels.. Thirty-two patients with diabetic proteinuria (>500 mg/day) with a normal glomerular filtration rate (GFR) and 33 healthy subjects were enrolled. Patients were treated with ramipril 5 mg daily for 2 months. Proteinuria, GFR, high-sensitivity C-reactive protein (hsCRP), visfatin, flow-mediated dilatation (FMD) and homeostasis model assessment of insulin resistance (HOMA-IR) index measurements were performed both before and after the treatment.. The plasma visfatin, and hsCRP levels of the patients were significantly higher and the FMD was significantly lower (P < 0.001 for all). The visfatin levels were significantly correlated to FMD, systolic and diastolic blood pressures, proteinuria, eGFR, HOMA-IR and hsCRP. Ramipril treatment resulted in a significant decrease in plasma visfatin, proteinuria, hsCRP, HOMA-IR and increase in FMD (P < 0.001) in patients (P < 0.001 for all).. The present study suggests that plasma visfatin levels are related to the endothelial functions, inflammation and the severity of proteinuria in diabetic nephropathy. Treatment with ramipril causes a significant decrease in visfatin levels along with the improvement of proteinuria, endothelial dysfunction and inflammatory state in diabetic nephropathy.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Blood Pressure; C-Reactive Protein; Cytokines; Diabetic Nephropathies; Endothelium, Vascular; Female; Glomerular Filtration Rate; Humans; Inflammation; Insulin Resistance; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Proteinuria; Ramipril; Renin-Angiotensin System; Time Factors; Treatment Outcome; Vasodilation

Plasma levels of the inflammatory biomarker C-reactive protein (CRP) predict cardiovascular risk and may represent a target for treating and/or monitoring risk-reduction strategies. The effect of angiotensin-converting enzyme inhibitors on CRP levels has not been adequately studied.. A total of 264 men and women, with CRP levels of 2 mg/L or greater and no history of cardiovascular disease, were enrolled in a 12-week randomized, double-blind, placebo-controlled study. Participants were randomly assigned to receive 10 mg/day of ramipril (n=132) or placebo (n=132) for 12 weeks. The main outcome measure was the change in CRP levels from baseline to 12 weeks in the ramipril- versus placebo treated patients.. The mean (+/- SD) age was 53+/-9 years (60% men). Baseline demographics were similar between the volunteers allocated to receive either placebo or ramipril. The geometric mean CRP at baseline was 3.84 mg/L (95% CI 3.62 mg/L to 4.06 mg/L). The percentage change in geometric mean CRP values over 12 weeks was --13.2% (95% CI --22.3% to --3.2% ) in the placebo group compared with --21.1% (95% CI --29.9% to --11.2%) in the ramipril group (P nonsignificant), indicating no significant reduction in the primary end point of the trial.. A 12-week ramipril treatment protocol for healthy middle-aged volunteers did not lower CRP levels compared with placebo. However, because of the inherent variability of CRP levels, a much larger study is required to exclude a small treatment effect.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; C-Reactive Protein; Confidence Intervals; Coronary Artery Disease; Double-Blind Method; Female; Health Status Indicators; Humans; Hypertension; Inflammation; Male; Middle Aged; Ramipril

We examined the relationship between glycemic control, vascular reactivity, and inflammation in type 2 diabetic subjects.. Thirty subjects with type 2 diabetes were initiated on intensive insulin therapy (continuous subcutaneous insulin infusion [n = 12] or multiple daily injections [n = 18]) and then randomized to either pioglitazone (PIO group;45 mg/day), ramipril (RAM group; 10 mg/day), or placebo (PLC group) for 36 weeks. Euglycemic-hyperinsulinemic clamp was used to quantify insulin resistance, and plethysmography was used to assess changes in forearm blood flow (FBF) after 1) 5 min of reactive hyperemia and 2) brachial artery infusion of acetylcholine (7.5, 15, and 30 microg/min) and sodium nitroprusside (3 and 10 microg/min).. The decreases in A1C (approximately 9.0-7.0%) and fasting plasma glucose (approximately 190-128 mg/dl) were equal in all groups. In the PIO group, glucose disposal increased from 3.1 to 4.7 mg x kg(-1) x min(-1), and there was a greater decrease in plasma triglycerides ( approximately 148 vs. 123 mg/dl) and free fatty acids (approximately 838 vs. 595 mEq/l) compared with the RAM or PLC groups (P < 0.05). Plasma adiponectin doubled with pioglitazone treatment (6.2 +/- 0.7 to 13.1 +/- 1.8 microg/ml), while endothelin-1 decreased only with ramipril treatment (2.5 +/- 0.2 to 1.1 +/- 0.2 pg/ml) (P < 001). The increase in FBF during reactive hyperemia (215%) and acetylcholine (from 132 to 205%, 216 to 262%, and 222 to 323%) was greater in the PIO versus RAM or PLC groups. In contrast, FBF during sodium nitroprusside treatment was greater in the RAM group (141-221% and 218-336%) compared with the PIO or PLC groups (all P < 0.05).. Addition of pioglitazone or ramipril to intensive insulin therapy in type 2 diabetes further improves vascular dysfunction. Pioglitazone enhances endothelial-mediated vasodilation, whereas ACE inhibition enhances endothelial-independent vasodilation. These different vascular effects, combined with the observation that pioglitazone decreases free fatty acids and triglycerides and increases adiponectin, while ramipril reduces endothelin-1, suggest that different mechanisms underlie the vascular responses.

Topics: Antihypertensive Agents; Blood Flow Velocity; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Therapy, Combination; Forearm; Glucose Clamp Technique; Glycated Hemoglobin; Hispanic or Latino; Humans; Hypoglycemic Agents; Inflammation; Insulin; Insulin Infusion Systems; Pioglitazone; Placebos; Ramipril; Thiazolidinediones

On-pump coronary artery bypass graft (CABG) surgery triggers an inflammatory response (IR) which may impair revascularization. The study aimed at (1) characterizing the temporal profile of the IR by assaying appropriate markers in both systemic and coronary blood, and (2) determining whether (and which doses of) cardiovascular drugs known to have antiinflammatory properties, namely statins and ACE-inhibitors (ACEI), inhibit the response.. Patients scheduled for CABG (n=22) were randomized to statin/ACEI combination treatment at standard doses (STD, ramipril 2.5/simvastatin 20 mg, or atorvastatin 10 mg), or at high doses (HiDo, ramipril 10 mg, or enalapril 20 mg/simvastatin 80 mg, or atorvastatin 40 mg). Plasma levels of interleukin 6, tumor necrosis factor alpha, E-selectin, von Willebrand factor (vWF), and sVCAM-1 were serially assayed (ELISA) before, during, and after CABG. Blood was drawn from an artery, a systemic vein, and the coronary sinus. Myocardial perfusion scans were obtained before and 2 months after surgery in 19 out of 22 subjects. In the STD group both IL-6 and TNF displayed striking increases which were similar at all sites and peaked 10 to 60 minutes after aortic declamping. Such increases were drastically attenuated in the HiDo group. Instead, only modest increases in venous E-selectin, vWF, and sVCAM-1 were observed. Scintigraphic ischemia scores were entirely normalized after versus before CABG in the HiDo but not in the STD treatment group.. On-pump CABG surgery is associated with an intense systemic inflammatory response, which can be almost completely prevented by early treatment with high (but not standard) doses of ACE-inhibitors and statins.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Atorvastatin; Coronary Artery Bypass; Coronary Artery Disease; Coronary Circulation; Creatine Kinase; Dose-Response Relationship, Drug; E-Selectin; Enalapril; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Inflammation Mediators; Interleukin-6; Leukocyte Count; Male; Middle Aged; Platelet Count; Pyrroles; Ramipril; Simvastatin; Stroke Volume; Time Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; von Willebrand Factor

Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, used alone or in combination, have been shown to improve outcomes in certain populations, primarily when administered in high doses. For stable coronary atherosclerotic disease, however, the relative physiologic effect of these therapies is unclear. Furthermore, because of the notorious subtarget dosing of such agents in clinical practice, we explored the influence of a modest dosing of an angiotensin-converting enzyme inhibitor, angiotensin II type 1 receptor blockers, and the combination on common biologic markers of coronary atherosclerotic disease.. This randomized, cross-over study enrolled stable coronary atherosclerotic disease patients (n=20), each receiving three treatments: candesartan 16 mg daily, ramipril 5 mg daily, and candesartan 8 mg plus ramipril 2.5 mg daily. Treatments were administered for 2 weeks with a 2-week washout. Blood samples were collected before and after each treatment. Markers of endothelial function, fibrinolytic balance, and vascular inflammation were measured.. No significant differences were observed in the pretreatment concentrations of angiotensin-converting enzyme or of any measured biologic marker. Relative to pretreatment levels, candesartan alone was the only therapy to exhibit an action on any measured biomarker--a trend toward increased nitric oxide concentrations (P=0.054). Otherwise, no effects on biologic markers were observed with the treatments.. This study of various methods of the renin-angiotensin system inhibition in stable coronary atherosclerotic disease patients demonstrates negligible effects of a modest dosing of ramipril and the combination of ramipril plus candesartan on common biologic markers of coronary atherosclerotic disease. Candesartan at modest doses may favorably influence endothelial function. Overall, however, the results indicate that the commonly practiced subtarget dosing of such treatments provides little, if any, benefit pertaining to key physiologic components of coronary atherosclerotic disease.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biomarkers; Biphenyl Compounds; Coronary Artery Disease; Cross-Over Studies; Drug Therapy, Combination; Endothelium, Vascular; Female; Fibrinolysis; Humans; Inflammation; Male; Middle Aged; Ramipril; Tetrazoles

The HOPE study was a 19 country, prospective randomized trial in which the ACE-inhibitor Ramipril but not Vitamin E significantly reduced the risk of future cardiovascular events in a high-risk population of men and women, including many with diabetes. The benefits were present in all sub-groups, independent of the presence or absence of diabetes, hypertension, evidence of cardiovascular disease, microalbuminuria, blood pressure lowering, the use of aspirin, lipid-lowering or antihypertensive medication. It provided clear evidence that Ramipril should safely and cost-effectively be used in individuals not known to have low ventricular ejection fraction or heart failure but at high-risk of cardiovascular events. It was also beneficial in patients with renal insufficiency, reducing progression of proteinuria and development of new microalbuminuria. It provided micro- and macrovascular benefits in people with diabetes, reduced the development of new cases of diabetes and showed a positive and graded association between the waist-to-hip ratio and the risk of developing diabetes. Sub-studies completed and on-going into the predictive role of natriuretic peptides, infectious and inflammatory markers, provide insight into possible mechanisms of action of Ramipril.

Topics: Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cost-Benefit Analysis; Diabetes Complications; Female; Heart Failure; Humans; Inflammation; Kidney Diseases; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Ramipril; Stroke; Ventricular Function, Left; Vitamin E

To evaluate the hypothesis that angiotensin-converting enzyme inhibitor therapy with ramipril reduces baseline levels of C-reactive protein in patients at high cardiovascular risk.. Secondary prevention patients were screened for eligibility and treated with ramipril for 6 month. Baseline and 6-month highly sensitive C-reactive protein levels were determined.. A total of 77 patients were analyzed. The median highly sensitive C-reactive protein concentration at baseline was 2.17 mg/l (interquartile interval 0.97-4.54); whereas in post-treatment, the median was 1.70 mg/l (interquartile interval 0.88-3.41), P=0.0009. Patients were stratified according to risk level determined by baseline highly sensitive C-reactive protein levels: low-risk (<1 mg/l), intermediate risk (1-3 mg/l) and high risk (>3 mg/l) The reduction in highly sensitive C-reactive protein occurred at the expense of the high-risk group (baseline 5.02 mg/l, post-treatment 3.3 mg/l, P<0.0001), with no differences in the other groups. In multiple regression analysis, the reduction observed in the high-risk group could not be explained by baseline treatment or change in any of the variables analyzed.. Highly sensitive C-reactive protein levels were reduced after a 6-month ramipril therapy in secondary prevention patients, suggesting an anti-inflammatory effect of angiotensin-converting enzyme inhibitors. Future investigations will be done to confirm these results, and to investigate how angiotensin-converting enzyme inhibitor treatment elicits anti-inflammatory effects.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; C-Reactive Protein; Cardiovascular Diseases; Drug Therapy, Combination; Female; Humans; Inflammation; Male; Middle Aged; Ramipril; Risk Factors; Secondary Prevention

The aim: To improve the effectiveness of treatment of patients with hypertension using metabolic therapy based on the evaluation of endothelial dysfunction indicators, markers of inflammation, and blood lipid spectrum.. Materials and methods: A clinical study was performed with 72 patients (34 male and 38 female) with stage 2 arterial hypertension of 2-3 degrees, admitted to the cardiology department of the municipal non-profit enterprise "Lviv Emergency Clinical Hospital". The mean age of patients was 44.8±8.5 years. Patients were divided into 2 groups: Group I was taking quercetin in addition to basic therapy (Ramipril/Amlodipine in individually adjusted dose); Group II - had basic therapy following the clinical protocol. The level of nitric oxide, IL-1, IL-6, TNF-a, CRP, seromucoid, blood lipid spectrum was determined.. Results: There is a significant decrease in the NO and CRP levels. There is a decrease in the TNF-a level by 31.27±2.13 (p<0.01) after the treatment of patients with hypertension. The TNF-a level decreased by 22.2±1.13 (p<0.01) with the use of basic therapy. IL-1 decreased significantly in the two groups, but it was more pronounced in group I, by 40.68±1.67 (p<0.01) and 21.4±2.1 in group II (p<0.05). There is a positive change in the blood lipid spectrum, but the changes were more pronounced in the group of patients receiving metabolic therapy.. Conclusions: The use of quercetin (Corvitin, Quertin) in combination therapy with the combined antihypertensive drug containing ramipril/amlodipine (Egis-Hungary) significantly reduces the levels of nitric oxide, CRP, IL-1, and blood lipid spectrum, which reduces the incidence of complications and progression of hypertension.

Topics: Adult; Amlodipine; Antihypertensive Agents; Blood Pressure; Female; Humans; Hypertension; Inflammation; Interleukin-1; Lipid Metabolism; Male; Middle Aged; Nitric Oxide; Quercetin; Ramipril

Experimental study.. To evaluate the efficacy of Angiotensin-converting enzyme inhibitor Ramipril, as a mitigator of radiation-induced spinal cord injury.. Stony Brook University, Stony Brook, NY, USA.. Total of 22 rats were irradiated with single doses of 23.6-33 Gy at the C4-T2 spinal levels. After irradiation, the rats were randomized to the radiation only control group and the Ramipril-treated (radiation + Ramipril) experimental group. Ramipril 1.5 mg/kg/day was given in the drinking water starting 1 week after radiation through the study duration.. All the rats irradiated with 28.5-33 Gy became paralyzed at 125 ± 4 days, whereas no rats became paralyzed after 23.6 Gy. The time to develop paralysis was delayed to 135 ± 4 days in Ramipril-treated group (P < 0.001). H&E and LFB showed microscopic structural restoration and remyelination with Ramipril treatment. VEGF expression was increased in the irradiated spinal cord, and the number of VEGF-positive cells was significantly decreased by Ramipril treatment (P < 0.001). Immunohistochemical stain with Iba-1 showed increased microglial infiltration in the irradiated spinal cords. The number of Iba-1-positive microglia was significantly reduced by Ramipril treatment (P < 0.05).. Ramipril reduced the rate of paralysis even at the paralysis-inducing radiation doses. It also significantly delayed the onset of paralysis. Neuroinflammation and endothelial cell damage may be the key mediators of radiation injury. Ramipril can be readily translatable to clinical application as a mitigatory of radiotherapeutic toxicity.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Calcium-Binding Proteins; Disease Models, Animal; Dose-Response Relationship, Radiation; Inflammation; Male; Microfilament Proteins; Microglia; Paralysis; Radiation Injuries, Experimental; Ramipril; Random Allocation; Rats, Inbred F344; Remyelination; Spinal Cord Injuries; Spinal Cord Regeneration

Hepatic fibrosis is a common feature of chronic liver injury, and the involvement of angiotensin II in such process has been studied earlier. We hypothesized that anti-angiotensin II agents may be effective in preventing hepatic fibrosis. In this study, Long Evans female rats were used and divided into four groups such as Group-I, Control; Group-II, Control + ramipril; Group-III, CCl4; and Group-IV, CCl4 + ramipril. Group II and IV are treated with ramipril for 14 d. At the end of treatment, the livers were removed, and the level of hepatic marker enzymes (aspartate aminotransferase, Alanine aminotransferase, and alkaline phosphatase), nitric oxide, advanced protein oxidation product , catalase activity, and lipid peroxidation were determined. The degree of fibrosis was evaluated through histopathological staining with Sirius red and trichrome milligan staining. Carbon-tetrachloride (CCl4) administration in rats developed hepatic dysfunction and raised the hepatic marker enzymes activities significantly. CCl4 administration in rats also produced oxidative stress, inflammation, and fibrosis in liver. Furthermore, angiotensinogen-inhibitor ramipril normalized the hepatic enzymes activities and improved the antioxidant enzyme catalase activity. Moreover, ramipril treatment ameliorated lipid peroxidation and hepatic inflammation in CCl4-treated rats. Ramipril treatment also significantly reduced hepatic fibrosis in CCl4-administered rats. In conclusion, our investigation suggests that the antifibrotic effect of ramipril may be attributed to inhibition of angiotensin-II mediated oxidative stress and inflammation in liver CCl4-administered rats.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Female; Inflammation; Liver Cirrhosis; Oxidative Stress; Ramipril; Rats; Rats, Long-Evans

Independent of their blood pressure lowering effect, ACE inhibitors are thought to reduce vascular inflammation. The clinical relevance of this effect is unclear with the current knowledge. Abdominal aortic aneurysms (AAA) are characterized by a broad, non-specific inflammatory response, and thus provide a clinical platform to evaluate the anti-inflammatory potential of ACE inhibitors.. Eleven patients scheduled for open AAA repair received ramipril (5 mg/day) during 2-4 weeks preceding surgery. Aortic wall samples were collected during surgery, and compared to matched samples obtained from a biobank. An anti-inflammatory potential was evaluated in a comprehensive analysis that included immunohistochemistry, mRNA and protein analysis. A putative effect of ACE inhibitors on AAA growth was tested separately by comparing 18-month growth rate of patients on ACE inhibitors (n = 82) and those not taking ACE inhibitors (n = 204). Ramipril reduces mRNA expression of multiple pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, TNF -α, Interferon-[Formula: see text], and MCP-1, as well as aortic wall IL-8 and MCP-1 (P = 0.017 and 0.008, respectively) protein content. The is followed by clear effects on cell activation that included a shift towards anti-inflammatory macrophage (M2) subtype. Evaluation of data from the PHAST cohort did not indicate an effect of ACE inhibitors on 18-month aneurysm progression (mean difference at 18 months: -0.24 mm (95% CI: -0.90-0.45, P = NS).. ACE inhibition quenches multiple aspects of vascular inflammation in AAA. However, this does not translate into reduced aneurysm growth.. Nederlands Trial Register 1345.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Aorta; Aortic Aneurysm, Abdominal; Blood Vessels; Female; Gene Expression Regulation; Humans; Inflammation; Interleukin-6; Interleukin-8; Macrophages; Male; Middle Aged; Ramipril; RNA, Messenger

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Inflammation; Male; Ramipril; Renal Dialysis; Tetrazoles; Valine; Valsartan

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature

This study compares the effect of two different strategies to inhibit the renin-angiotensin system in the setting of acute myocardial infarction (MI). Male Wistar rats were treated with placebo, the angiotensin-converting enzyme (ACE) inhibitor ramipril (1 mg/kg/day), or the AT1 receptor antagonist, olmesartan (1 mg/kg/day), both initiated 1 week before induction of MI and continued for 6 weeks after MI. The inflammatory reaction in the heart was investigated 7 days post-MI by determination of macrophage infiltration and the expression of tumor necrosis factor (TNF-alpha), interleukin (IL)-1beta and IL-6 at mRNA and protein levels. Six weeks post-MI, cardiac function was measured following chronic implantation of catheters in the LV and femoral artery, and cardiac morphology and coronary structure were investigated in picrosirius-red stained hearts. In placebo-treated rats, macrophage infiltration was accompanied by upregulation of IL-1beta and IL-6 mRNA in the peri-infarct zone. TNF-alpha and IL-1beta mRNA and protein were also upregulated in the non-infarcted myocardium. Whereas both treatment regimes significantly reduced IL-6 upregulation, olmesartan additionally reduced macrophage infiltration and IL-1beta expression. Six weeks post-MI, placebo-treated MI animals developed an impaired cardiac function with structural remodeling of the myocardium and coronaries. While olmesartan and ramipril both improved cardiac function and reduced infarct size and myocardial/coronary remodeling, olmesartan was more effective not only in increasing vascular perimeter, inner vascular diameter and septal thickness but also in lowering media thickness of coronary arteries, inner left ventricular diameter, left ventricular circumference and left ventricular end-diastolic pressure than ramipril. Thus, following MI the AT1 receptor blocker, olmesartan, attenuated cardiac inflammatory reactions and protected myocardial/coronary structure and function of the failing heart proving to be of similar, in some cases superior effectiveness in this respect than the ACE inhibitor, ramipril.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Cardiovascular Diseases; Cardiovascular System; Disease Models, Animal; Dose-Response Relationship, Drug; Imidazoles; Inflammation; Interleukin-1; Interleukin-6; Male; Myocardial Infarction; Placebos; Ramipril; Rats; Rats, Wistar; Renin-Angiotensin System; RNA, Messenger; Tetrazoles; Tumor Necrosis Factor-alpha

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cilazapril; Enalaprilat; Erythema; Female; Guinea Pigs; Inflammation; Ramipril

Paw oedema in the rat by carrageenin and kaolin partially caused by Hageman factor activation was potentiated by the new angiotensin converting enzyme (ACE) inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl-L-alanyl]-(lS,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid] (ramipril, Hoe 498) due to its inhibition of kininase II which results in increased bradykinin levels. A dose of 1 microgram ramipril injected into the hind paw of Sprague-Dawley rats concomitantly with, or 1 mg/kg given orally 30 min before administration of the irritants, led to significantly increased inflammatory reactions. The same effects were observed when ramipril was administered 3 h after carrageenin. In the kallikrein-kinin-deficient Brown-Norway rat strain Mai Pfd/f, ramipril did not significantly alter the paw oedema induced as described above. In addition, pretreatment of Sprague-Dawley rats with 10 mg/kg i.v. bromelains completely prevented the potentiation of inflammation by ramipril. Paw oedema provoked by the Hageman factor non-activators serotonin, dextran, ovalbumin and anti-rat IgG was not potentiated by ramipril. The chronic adjuvant arthritis in Lewis rats was not influenced by daily oral treatment with 0.1-3 mg/kg ramipril. Thus, in the rat only those inflammatory reactions involving kinins, presumably generated by Hageman factor activators, are potentiated by ramipril and presumably by other ACE-inhibitors.

Topics: Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Animals; Arthritis; Arthritis, Experimental; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Disease Models, Animal; Inflammation; Male; Ramipril; Rats; Rats, Inbred Strains