Tissue distribution of antihypertensive dipeptide, Val-Tyr, after its single oral administration to spontaneously hypertensive rats
Tissue distribution of antihypertensive dipeptide, Val-Tyr, after its single oral administration to spontaneously hypertensive rats
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DOI：
10.1002/psc.568
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发表时间：
2004-09-01
影响因子：
2.1
通讯作者：
Matsumoto, K
中科院分区：
文献类型：
--
作者：
Matsui, T;Imamura, M;Matsumoto, K
本文研究了抗高血压二肽Val-Tyr(VY)在自发性高血压大鼠(SHR)组织中的分布。18周龄SHR单次口服VY(10 mg/kg)后，收缩压持续下降9h(SBP0h 198.0+/-3.6mmHg；SBP9h 154.6+/-3.5mmHg)。VY测定的结果是，血浆VY水平在1h比0h升高约10倍，此后迅速下降。在组织中，VY在肾、肺、心脏、肠系膜动脉和腹主动脉广泛蓄积，9h以上的曲线下面积大于40pmolh/g组织，其中以肾和肺的VY水平较高。此外，每个组织的平均停留时间(MRT；5小时，肝脏除外)表明，VY较好地累积在组织中，而不是在血浆中(MRT 3.8小时)。腹主动脉和肾脏组织血管紧张素I转换酶活性和血管紧张素II水平显著降低，提示这些器官可能是VY降压作用的靶点。版权所有(C)2004欧洲肽协会和John Wiley Sons，Ltd.
The distribution of an antihypertensive dipeptide, Val-Tyr (VY), in the tissues of spontaneously hypertensive rats (SHR) was investigated in this study. A single oral administration of VY (10 mg/kg) to 18-week-old SHR resulted in a prolonged reduction of systolic blood pressure (SBP) up to 9 h (SBP0h 198.0 +/- 3.6 mmHg; SBP9h 154.6 +/- 3.5 mmHg). As a result of VY determination, a roughly 10-fold higher increment of plasma VY level was observed at 1 h than that at 0 h, whereas thereafter the level declined rapidly. In tissues, VY was widely accumulated in the kidney, lung, heart, mesenteric artery and abdominal aorta with the area under the curve over 9 h of more than 40 pmol h/g tissue; of these a higher VY level was observed in the kidney and lung. In addition, a mean resident time (MRT) for each tissue (>5 h except for liver) revealed that VY preferably accumulated in the tissues rather than in the plasma (MRT 3.8 h). Significant reductions of tissue angiotensin I-converting enzyme activity and angiotensin II level were found in the abdominal aorta as well as in the kidney, suggesting that these organs could be a target site associated with the antihypertensive action of VY. Copyright (C) 2004 European Peptide Society and John Wiley Sons, Ltd.