Takakura S, Furuichi Y, Yamamoto T, Ogawa T, Satoh H, Mori J
Department of Pharmacology, Fujisawa Pharmaceutical Co, Ltd, Osaka, Japan.
Stroke. 1994 Mar;25(3):677-82; discussion 682-3. doi: 10.1161/01.str.25.3.677.
Several types of antihypertensive drugs have been reported to protect stroke-prone spontaneously hypertensive rats from stroke. However, the clinical relevance remains unclear. This study was performed to investigate the effect of nilvadipine, a calcium channel blocker, on the development of neurological deficits in stroke-prone spontaneously hypertensive rats. In addition, plasma levels of nilvadipine were measured to determine the clinical relevance.
Salt-loaded stroke-prone spontaneously hypertensive rats were orally administered nilvadipine mixed with a powder diet (0.01% and 0.03%, wt/wt). Non-salt-loaded rats were maintained on tap water. Chronological changes in neurological deficit scores and systolic blood pressure were recorded. After 6 weeks of medication, measurement of plasma levels of nilvadipine, serum biochemical analysis, and pathological observation of both the brain and the kidney were performed.
In the salt-loaded control group, both severe hypertension and neurological deficit developed, and the final survival rate was 30%. Systolic blood pressure decreased significantly in the high-dose nilvadipine-treated group but not in the low-dose nilvadipine-treated group. However, the development of neurological deficit was almost completely inhibited in both nilvadipine-treated groups that had no deaths (P < .01). The mean plasma levels of nilvadipine in the low-dose group and in the high-dose group at the time of death were 0.21 ng/mL and 0.61 ng/mL, respectively.
Nilvadipine inhibited the development of neurological deficit in stroke-prone spontaneously hypertensive rats at plasma concentrations lower than that in clinical use. Thus, nilvadipine might prevent cerebral vascular disorders at doses routinely used for essential hypertension.
据报道，几种类型的抗高血压药物可保护易发生中风的自发性高血压大鼠预防中风。然而，其临床相关性仍不明确。本研究旨在探讨钙通道阻滞剂尼伐地平对易发生中风的自发性高血压大鼠神经功能缺损发展的影响。此外，还测量了尼伐地平的血浆水平以确定其临床相关性。
给高盐饲养的易发生中风的自发性高血压大鼠口服与粉末饲料混合的尼伐地平（0.01%和0.03%，重量/重量）。非高盐饲养的大鼠饮用自来水。记录神经功能缺损评分和收缩压的时间变化。用药6周后，进行尼伐地平血浆水平测定、血清生化分析以及脑和肾的病理观察。
在高盐饲养的对照组中，出现了严重高血压和神经功能缺损，最终存活率为30%。高剂量尼伐地平治疗组的收缩压显著降低，而低剂量尼伐地平治疗组则未降低。然而，在两个无死亡的尼伐地平治疗组中，神经功能缺损的发展几乎完全受到抑制（P <.01）。低剂量组和高剂量组死亡时尼伐地平的平均血浆水平分别为0.21 ng/mL和0.61 ng/mL。
尼伐地平在低于临床使用浓度的血浆浓度下即可抑制易发生中风的自发性高血压大鼠神经功能缺损的发展。因此，尼伐地平可能在用于原发性高血压的常规剂量下预防脑血管疾病。
