Different effects of perindopril and enalapril on monocyte cytokine release in coronary artery disease patients with normal blood pressure

摘要

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-??, interleukin-1?? 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 antiinflammatory 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.