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KMID : 0043319960190050390
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Archives of Pharmacal Research
1996 Volume.19 No. 5 p.390 ~ p.395
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Effects of Subchronic Treatment with AT1 Receptor Antagonists on Endothelium-dependent and -independent Relaxatio
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Lee Byung-Ho
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Abstract
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To investigate whether receptor antagonists are acting by increasing endothelium-de-pendent and -independent relaxation of aortas in normotensive rats, 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 $pD_{2}$ of KR-30988 for ACh-induced relaxation was 8.33 0.16, significantly (p <0.05) lower than that of control group . ACh-induced relaxation was significantly increased on losartan-treated group (p<0.01) at M of ACh, and in captopril-treated group (p<0.05) at the range of M of ACh. The values for histamine-induced relaxatio 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 ( M), and completely bolcked by pretreatment of L-NAME in all groups. Sodium nitroprusside-induced relaxations were not significantly changed by all drugs tested in this experiments. These results suggest that receptor antagonists, losartan and KR-30988, enhance the endothelium-dependent relaxatio on aortic preparations through the release of, or increase sensitivity, to nitric oxide in nor-motensive rats.
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KEYWORD
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AT1 receptor, Losartan, KR-30988, Endothelium-dependent relaxation
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