ramipril and Vasculitis

The excess in cardiovascular risk in patients with rheumatoid arthritis provides a strong rationale for early therapeutical interventions. In view of the similarities between atherosclerosis and rheumatoid arthritis and the proven benefit of angiotensin-converting enzyme inhibitors in atherosclerotic vascular disease, it was the aim of the present study to delineate the impact of ramipril on endothelial function as well as on markers of inflammation and oxidative stress in patients with rheumatoid arthritis.. Eleven patients with rheumatoid arthritis were included in this randomized, double-blind, crossover study to receive ramipril in an uptitration design (2.5 to 10 mg) for 8 weeks followed by placebo, or vice versa, on top of standard antiinflammatory therapy. Endothelial function assessed by flow-mediated dilation of the brachial artery, markers of inflammation and oxidative stress, and disease activity were investigated at baseline and after each treatment period. Endothelial function assessed by flow-mediated dilation increased from 2.85+/-1.49% to 4.00+/-1.81% (P=0.017) after 8 weeks of therapy with ramipril but did not change with placebo (from 2.85+/-1.49% to 2.84+/-2.47%; P=0.88). Although systolic blood pressure and heart rate remained unaltered, diastolic blood pressure decreased slightly from 78+/-7 to 74+/-6 mm Hg (P=0.03). Tumor necrosis factor-alpha showed a significant inverse correlation with flow-mediated dilation (r=-0.408, P=0.02), and CD40 significantly decreased after ramipril therapy (P=0.049).. Angiotensin-converting enzyme inhibition with 10 mg/d ramipril for 8 weeks on top of current antiinflammatory treatment markedly improved endothelial function in patients with rheumatoid arthritis. This finding suggests that angiotensin-converting enzyme inhibition may provide a novel strategy to prevent cardiovascular events in these patients.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Arthritis, Rheumatoid; Atherosclerosis; Biomarkers; Cells, Cultured; Cross-Over Studies; Endothelial Cells; Female; Humans; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Oxidative Stress; Ramipril; Renin-Angiotensin System; Risk Factors; Treatment Outcome; Umbilical Veins; Vasculitis; Vasodilation

Angiotensin (Ang) II is now recognized to be a mediator of a wide variety of inflammatory processes. This study investigated renin-angiotensin system (RAS) components and a number of inflammatory mediators in left ventricular biopsies from 2-vessel disease unstable angina (UA) (n=43) and stable angina (SA) (n=15) patients undergoing coronary bypass surgery. Biopsy samples from 6 patients undergoing valve replacement for mitral stenosis served as controls. UA patients were randomly assigned to angiotensin-converting enzyme (ACE)-inhibitor (ramipril), AT1 antagonist (valsartan), or placebo and treated during the 5 days preceding coronary bypass surgery, performed from 6 to 9 days after coronary angiography. During coronary angiography coronary blood flow was measured and samples were obtained from aorta and coronary sinus for determination of Ang I and Ang II gradients. The hearts of UA patients produced Ang II in a greater amount than in SA patients (P<0.01). UA biopsy samples showed numerous DR+ cells, identified as lymphocytes, macrophages, and endothelial cells. Reverse-transcriptase polymerase chain reaction showed overexpression of AGTN, ACE, and AT1-R genes, as well as upregulation of TNF-alpha, IL-6, IFN-gamma, and iNOS genes (P<0.01), with no differences between nonischemic and potentially ischemic areas. AGTN, ACE, and cytokine genes were mainly localized on endothelial cells. Ramipril and valsartan markedly decreased the expression levels of TNF-alpha, IL-6, and iNOS, and, to a lesser extent, of IFN-gamma genes, but did not affect the number of DR+ cells, with no significant difference between the 2 treatments. These results show that locally generated Ang II amplifies the immunomediated inflammatory process of coronary microvessels occurring in unstable angina.

Topics: Adult; Aged; Angina Pectoris; Angina, Unstable; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Chymases; Combined Modality Therapy; Coronary Angiography; Coronary Artery Bypass; Coronary Circulation; Cytokines; Female; Gene Expression Profiling; Humans; Male; Microcirculation; Middle Aged; Mitral Valve Stenosis; Myocardium; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Preoperative Care; Ramipril; Renin-Angiotensin System; RNA, Messenger; Serine Endopeptidases; Tetrazoles; Valine; Valsartan; Vasculitis

Topics: Angiotensin-Converting Enzyme Inhibitors; Arthritis, Rheumatoid; Atherosclerosis; Humans; Ramipril; Risk Factors; Vasculitis

Propylthiouracil is a drug used in the treatment of hyperthyroidism for more than 60 years. Adverse side effects are seen in 1-5% of patients. Renal complications of the drug including glomerulonephritis and vasculitis are rarely seen. Cases of propylthiouracil-induced rapidly progressive glomerulonephritis and vasculitis are reported in association with antineutrophil cytoplasmic autoantibodies. Here we report a case of positive antineutrophil cytoplasmic autoantibodies rapidly progressive glomerulonephritis (RPGN) associated with propylthiouracil treatment.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Antineutrophil Cytoplasmic; Atrophy; Humans; Hyperthyroidism; Kidney; Kidney Glomerulus; Male; Propranolol; Propylthiouracil; Ramipril; Vasculitis