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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1299.)
© 2002 American Heart Association, Inc.

Vascular Biology

Beneficial Effects of Combined Blockade of ACE and AT₁ Receptor on Intimal Hyperplasia in Balloon-Injured Rat Artery

Shokei Kim; Yasukatsu Izumi; Yasuhiro Izumiya; Yumei Zhan; Masaru Taniguchi; Hiroshi Iwao

From the Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.

Correspondence to Shokei Kim, MD, PhD, Department of Pharmacology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. E-mail kims{at}med.osaka-cu.ac.jp

Objective— The present study was undertaken to elucidate the effect of the ACE inhibitor and the angiotensin II type 1 (AT₁) receptor antagonist in combination on neointimal hyperplasia after balloon injury.

Methods and Results— Temocapril (an ACE inhibitor), CS-866 (an AT₁ receptor antagonist), or their combination was given orally to rats, and their effects were compared on vascular hyperplasia induced by balloon injury. The maximal preventive effect of temocapril and CS-866 alone on neointimal thickening after balloon injury was obtained at a dose of 20 and 10 mg/kg per day, respectively. However, compared with either agent alone, combined temocapril and CS-866 (20 and 10 mg/kg per day, respectively) prevented intimal thickening to a larger extent. Furthermore, compared with either agent alone, combined temocapril and CS-866 prevented vascular smooth muscle cell proliferation in the intima more potently. The increase in platelet-derived growth factor receptor tyrosyl phosphorylation was reduced more potently by the combination of both agents compared with either agent alone. The nonpeptide bradykinin B₂ receptor antagonist or the NO synthase inhibitor reduced the prevention of intimal thickening by combined temocapril and CS-866.

Conclusions— Compared with either agent alone, the combination of an ACE inhibitor and an AT₁ receptor antagonist is more effective in the prevention of vascular hyperplasia due to bradykinin or NO.

Key Words: balloon injury • intimal thickening • angiotensin • angiotensin-converting enzyme • combination therapy

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