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Effects of subchronic treatment with AT1 receptor antagonists on endothelium-dependent and-independent relaxation

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Abstract

To investigate whether AT1 receptor antagonists are acting by increasing endothelium-dependent and-independent relaxation of aortas in normotensive rats, AT1 receptor antagonists, losartan and KR-30988, and angiotensin converting enzyme inhibitor, captopril, were orally administered for two weeks (50 mg/kg, b.i.d.). The blood pressure, heart rate and body weight were not significantly changed by losartan, KR-30988 and captopril compared to the control group. In aortic preparations, the pD2 of KR-30988 for ACh-induced relaxation was 8.33±0.16, significantly (p<0.05) lower than that of control group (7.71±0.15). ACh-induced relaxation was significantly increased in losartan-treated group (p<0.01) at 10−6 M of ACh, and in captopril-treated group (p<0.05) at the range of 10−7–10−5 M of ACh. The pD2 values for histamine-induced relaxation of losartan, KR-30988 and captopril were 5.57±0.10, 5.85±0.21 and 5.60±0.01, respectively, with significant differences in all groups (p<0.01) compared to that of control group (5.13±0.09). ACh-induced relaxations of aortic preparations were not changed by pretreatment of indomethacin (10−5 M), and completely blocked by pretreatment of L-NAME (10−5 M) in all groups. Sodium nitroprusside-induced relaxations were not significantly changed by all drugs tested in this experiments. These results suggest that AT1 receptor antagonists, losartan and KR-30988, enhance the endothelium-dependent relaxation on aortic preparations through the release of, or increase sensitivity, to nitric oxide in normotensive rats.

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  1. Pharmaceutical Screening Research Laboratory, Korea Research Institute of Chemical Technology, Yusong, P.O. Box 107, 305-606, Taejon, Korea

    Byung Ho Lee

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Lee, B.H. Effects of subchronic treatment with AT1 receptor antagonists on endothelium-dependent and-independent relaxation. Arch. Pharm. Res. 19, 390–395 (1996). https://doi.org/10.1007/BF02976384

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  • DOI: https://doi.org/10.1007/BF02976384

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