Effect of amlodipine and cilazapril treatment on platelet Ca2+ handling in spontaneously hypertensive rats.
Effect of amlodipine and cilazapril treatment on platelet Ca2+ handling in spontaneously hypertensive rats.
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DOI：
10.1291/hypres.26.901
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发表时间：
2003-11
期刊：
影响因子：
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通讯作者：
T. Oshima;N. Ono;R. Ozono;Y. Higashi;M. Ishida;T. Ishida;N. Miho;H. Nakashima;Y. Yano;M. Kambe
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文献类型：
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作者：
T. Oshima;N. Ono;R. Ozono;Y. Higashi;M. Ishida;T. Ishida;N. Miho;H. Nakashima;Y. Yano;M. Kambe
在自发性高血压大鼠（SHR）和原发性高血压患者的血小板中发现了异常的Ca 2+处理和增强的聚集反应，并被认为参与了高血压靶器官损害的进展。抗高血压治疗是否能改善高血压患者血小板反应异常是一个重要的研究课题。我们研究了抗高血压治疗如顺铂和西拉普利对SHR血小板中Ca 2+处理和聚集反应的影响。将4周龄雄性SHR分为3组。每组用氨碘平（A：10 mg/kg/天）、西拉普利（C：10 mg/kg/天）或媒介物（V）经管饲处理8周。于12周龄时，用Fura-2法测定各组SHR和同龄WKY大鼠（正常对照组）血小板[Ca 2 +]i。西拉普利和西拉普利治疗组的收缩压与WKY相似，并显著低于载体治疗组（分别为A：124 +/- 9，C：126 +/- 9，WKY：122 +/- 10和V：180 +/- 9 mmHg）。SHR三组基础[Ca ~（2+）]i相似，均高于WKY（A：47 +/- 1.7，C：47 +/- 1.2，V：48 +/- 3.9，WKY：40 +/- 4.0 nmol/l）。凝血酶（0.1U/ml）刺激的[Ca ~（2+）]i升高在SHR三组间无显著性差异，均高于WKY。通过离子霉素刺激评估的细胞内Ca 2+放电容量在所有组中相似。凝血酶诱导的最大血小板聚集反应在SHR的三个组相似，并高于WKY。Ca ~（2+）拮抗剂或ACE抑制剂降压治疗对SHR血小板内Ca ~（2+）代谢无明显影响。这些结果支持了SHR血小板中异常的Ca ~（2+）处理是由遗传决定的，并且不能通过药物治疗得到改善的假设。
Abnormal Ca2+ handling and enhanced aggregation response have been reported in platelets from spontaneously hypertensive rats (SHR) and patients with essential hypertension, and thought to be involved in the progression of target organ damage of hypertension. It is important to examine whether antihypertensive therapy can improve the abnormal platelet response in hypertension. We investigated the effect of antihypertensive treatment such as amlodipine and cilazapril on Ca2+ handling and aggregation response in SHR platelets. Four-week-old male SHR were divided into three groups. Each group was treated with amiodipine (A: 10 mg/kg/day), cilazapril (C: 10 mg/kg/day) or vehicle (V) for 8 weeks by gavage. At 12-week-old, platelet [Ca2+]i was measured with fura-2 in each group of SHR and age-matched Wistar-Kyoto rats (WKY) as normal control. Systolic blood pressure in amlodipine and cilazapril treated groups were similar with WKY and significantly lower than vehicle treated group (A: 124 +/- 9, C: 126 +/- 9, WKY: 122 +/- 10 and V: 180 +/- 9 mmHg, respectively). The basal [Ca2+]i in the three groups of SHR were similar and higher than WKY (A: 47 +/- 1.7, C: 47 +/- 1.2, V: 48 +/- 3.9 and WKY: 40 +/- 4.0 nmol/l, respectively). There were no significant differences in thrombin (0.1 U/ml)-stimulated [Ca2+]i rise in the presence or absence of extracellular Ca2+ among the three groups of SHR and these were higher than WKY. Intracellular Ca2+ discharge capacity, assessed by the ionomycinstimulation was similar in the all groups. Thrombin-induced maximum platelet aggregation responses in the three groups of SHR were similar and higher than WKY. The antihypertensive treatment of Ca2+ antagonist or ACE inhibitor gave no change in intraplatelet Ca2+ metabolism in SHR. These results support the hypothesis that an abnormal Ca2+ handling in SHR platelet is genetically determined and not improved by hypotensive therapy.