钙拮抗剂贝尼地平对实验性糖尿病患者尿激肽释放酶排泄及肾功能损害的影响

Effects of benidipine, a calcium antagonist, on urinary kallikrein excretion and renal impairment in experimental diabetes.

作者信息

Yoshida K, Kohzuki M, Yasujima M, Kanazawa M, Abe K

机构信息

Second Department of Internal Medicine, Tohoku University, School of Medicine, Sendai, Japan.

出版信息

J Hypertens. 1996 Feb;14(2):215-22. doi: 10.1097/00004872-199602000-00010.

DOI:10.1097/00004872-199602000-00010

PMID:8728299

Abstract

OBJECTIVE

To assess the long-term effects of different antihypertensive agents on urinary protein excretion and kallikrein excretion in diabetic rats with renal impairment.

METHODS

Uninephrectomized streptozotocin diabetic Wistar-Kyoto rats were randomly assigned to receive vehicle, a calcium antagonist (benidipine) or an angiotensin converting enzyme inhibitor (captopril) for up to 12 weeks. Active kallikrein was determined by its kininogenase activity, and generated kinins were measured by radioimmunoassay. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin.

RESULTS

Urinary protein excretion increased significantly in diabetic rats compared with non-diabetic rats. Urinary active kallikrein excretion was significantly reduced in diabetic rats, whereas urinary total kallikrein excretion was unchanged, resulting in a reduced percentage of active to total kallikrein compared with that in non-diabetic rats. Benidipine and captopril reduced blood pressure and attenuated the development of diabetic renal impairment in a similar manner. However, only benidipine attenuated the decreases in urinary active kallikrein excretion and the ratio of active to total kallikrein in diabetic rats.

CONCLUSIONS

Although pathophysiological relevance of impaired urinary kallikrein activation to the development of diabetic renal impairment remains to be determined, our result might suggest a new mechanism by which calcium antagonists protect the kidney from diabetic renal impairment.

摘要

目的

评估不同降压药物对肾功能受损的糖尿病大鼠尿蛋白排泄和激肽释放酶排泄的长期影响。

方法

将单侧肾切除的链脲佐菌素诱导的糖尿病Wistar-Kyoto大鼠随机分组，分别给予赋形剂、钙拮抗剂（贝尼地平）或血管紧张素转换酶抑制剂（卡托普利），持续12周。通过其激肽原酶活性测定活性激肽释放酶，并通过放射免疫测定法测量生成的激肽。在用胰蛋白酶激活无活性激肽释放酶后，通过测量激肽原酶活性来测定总激肽释放酶。

结果

与非糖尿病大鼠相比，糖尿病大鼠的尿蛋白排泄显著增加。糖尿病大鼠的尿活性激肽释放酶排泄显著减少，而尿总激肽释放酶排泄未改变，导致与非糖尿病大鼠相比，活性激肽释放酶占总激肽释放酶的百分比降低。贝尼地平和卡托普利以相似的方式降低血压并减轻糖尿病性肾损伤的发展。然而，只有贝尼地平减轻了糖尿病大鼠尿活性激肽释放酶排泄的减少以及活性激肽释放酶与总激肽释放酶的比率。