title: Different effects of perindopril and enalapril on monocyte cytokine release in coronary artery disease patients with normal blood pressure.
abstract: BACKGROUND
  Favorable effects of angiotensin-converting enzyme (ACE) inhibitor treatment on the incidence of cardiovascular and cerebrovascular mortality and morbidity are not limited to patients with elevated blood pressure. As suggested by our previous results, the physicochemical and pharmacokinetic differences between drugs may markedly contribute to the strength of pleiotropic effects of ACE inhibitors.
  
  
  METHODS
  The present study was aimed at comparing the effects of serum- and tissue-type ACE inhibitors on monocyte release of proinflammatory cytokines in normotensive patients with stable coronary artery disease. The participants were randomized to 90-day treatment with enalapril (20 mg daily, n = 29), perindopril (4 mg daily, n = 27) or placebo (n = 28). Plasma levels of lipids, glucose, insulin and high sensitivity C-reactive protein (hsCRP), as well as monocyte release of proinflammatory cytokines were determined before and after 30 days of therapy, and at the end of the treatment.
  
  
  RESULTS
  Lipopolysaccharide-stimulated monocytes from normotensive patients with stable coronary artery disease released significantly more TNF-α, interleukin-1β and monocyte chemoattractant protein-1 in comparison with monocytes from 23 matched control subjects. Their baseline hsCRP levels were also higher. Perindopril reversed the disease-induced changes in cytokine release and reduced plasma hsCRP, while the effect of enalapril was much more limited. The effect on both drugs on cytokine release was stronger in insulin-resistant than insulin-sensitive subjects.
  
  
  CONCLUSIONS
  Our results indicate that perindopril is superior to enalapril in producing monocyte-suppressing and systemic anti-inflammatory effects in normotensive patients with coronary artery disease. This action may contribute to the clinical effectiveness of tissue ACE inhibitors in the therapy of atherosclerosis-related disorders, particularly in insulin-resistant subjects.
authors: Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland. r.krysiak@interia.pl
authors: Robert
authors: R
authors: Krysiak
authors: Bogusław
authors: B
authors: Okopień
mesh_terms: D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016207:Cytokines / Q000097:blood*; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D020913:Perindopril / Q000627:therapeutic use*; D011044:Poland; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D001786:Blood Glucose; D016207:Cytokines; D018836:Inflammation Mediators; D008055:Lipids; D004656:Enalapril; D020913:Perindopril