Combined Treatment with an AT1 Receptor Blocker and Angiotensin Converting Enzyme Inhibitor Has an Additive Effect on Inhibiting Neointima Formation via Improvement of Nitric Oxide Production and Suppression of Oxidative Stress

DOI PubMed 被引用文献8件 参考文献58件
  • YAGI Shinji
    These authors contributed equally to this study
  • MORITA Toshisuke
    Department of Laboratory Medicine, Toho University School of Medicine These authors contributed equally to this study
  • KATAYAMA Shigehiro
    Fourth Department of Internal Medicine, Saitama Medical School

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Accumulating evidence shows that inhibition of the vascular renin-angiotensin system results in suppression of injury-elicited neointima formation. We attempted to determine whether or not combined treatment with an angiotensin II type 1 receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) has an additive inhibitory effect on balloon-injury-elicited neointima formation in the carotid artery. Male Sprague-Dawley rats were treated with an ARB (valsartan: 3 mg/kg/day) and/or an ACEI (benazepril: 0.3 mg/kg/day) from 1 week before until 2 weeks after balloon injury. Experiments were also conducted with one-third of the dose combination used in the original experiments. Both ARB and ACEI inhibited neointima formation without any blood pressure changes. The full-dose combination lowered blood pressure and suppressed neointima formation significantly compared with the levels in the groups treated with either ACEI or ARB alone. The low-dose combination without blood pressure reduction also inhibited neointima formation to a similar extent as the full-dose combination. We measured 8-iso-prostaglandin F2α (8-iso-PGF2α), a marker of oxidative stress, and nitrite and nitrate (NOx), an index of nitric monoxide production, in media conditioned by the injured artery. NOx production was lower and 8-iso-PGF2α was higher in the media of the injured artery, compared with those in the normal artery. ACEI restored NOx production more dramatically than ARB, and ARB suppressed 8-iso-PGF2α markedly compared with ACEI. These results suggest that the combination of an ARB and an ACEI exerts an additive inhibitory effect, presumably through an increase in production and bioavailability of NO from the endothelium. (Hypertens Res 2004; 27: 129-135)

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