Benidipine improves endothelial function in renal resistance arteries of hypertensive rats
Benidipine improves endothelial function in renal resistance arteries of hypertensive rats
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DOI：
10.1161/01.hyp.28.1.58
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发表时间：
1996-07-01
期刊：
影响因子：
8.3
通讯作者：
Sato, K
中科院分区：
文献类型：
--
作者：
Dohi, Y;Kojima, M;Sato, K
我们研究了长期降压治疗对自发性高血压大鼠(SHR)肾阻力动脉内皮功能的影响。Wistar-京都大鼠(WKY)作为正常血压参照物。成年自发性高血压患者使用贝尼地平(一种钙拮抗剂)或依卡拉津(一种血管扩张剂)治疗10周；这两种药物对血压的影响相似。记录肾动脉三级分支制备的环的等长张力变化。在去甲肾上腺素收缩的环上，乙酰胆碱引起的内皮依赖性舒张作用在SHR比WKY小。环氧合酶抑制剂甲氯芬酸的体外治疗不能改变松弛的差异，贝地平可改善受损的松弛，而依卡拉津无明显作用。在甲氯芬酸存在下，N-奥米伽-硝基-L-精氨酸甲酯对SHR的松弛有轻微的抑制作用；SHR的松弛比WKY的小，且不受贝尼地平的影响。在40 mmol/L KCl4收缩环上，甲氯芬酸对乙酰胆碱的松弛作用小于去甲肾上腺素收缩环。SHR的松弛程度小于WKY，但经贝尼地平治疗后恢复正常。因此，乙酰胆碱通过从自发性高血压大鼠受损的内皮释放一氧化氮和内皮衍生超极化因子来松弛大鼠肾脏阻力动脉。贝尼地平长期治疗可通过增强一氧化氮介导的松弛改善自发性高血压患者受损的松弛。
We studied the effects of long-term antihypertensive treatment on endothelial function in renal resistance arteries from spontaneously hypertensive rats (SHR). Wistar-Kyoto rats (WKY) were used as a normotensive reference. Adult SHR were treated with benidipine (a calcium antagonist) or ecarazine (a vasodilator) for 10 weeks; the drugs caused similar reductions in blood pressure. Changes in isometric tension of rings prepared from the third-order branches of the renal arteries were recorded. Endothelium-dependent relaxations induced by acetylcholine in rings contracted with norepinephrine were smaller in SHR than in WKY. The impaired relaxation was improved by benidipine treatment, but ecarazine had no significant effect, In vitro treatment with meclofenamic acid, a cyclooxygenase inhibitor, did not alter the differences in the relaxations. In the presence of meclofenamic acid, N-omega-nitro-L-arginine methyl ester slightly reduced the relaxations; the relaxation was smaller in SHR than in WKY and was not affected by benidipine treatment. In rings contracted with 40 mmol/L KCl, the relaxations induced by acetylcholine in the presence of meclofenamic acid were smaller than those in rings contracted with norepinephrine. The relaxation was smaller in SHR than in WKY but was normalized by benidipine treatment. Thus, acetylcholine relaxes rat renal resistance arteries by releasing nitric oxide and endothelium-derived hyperpolarizing factor from the endothelium which is impaired in SHR. Long-term benidipine treatment improves the impaired relaxation in SHR by enhancing nitric oxide-mediated relaxation.