自发性高血压大鼠和醋酸脱氧皮质酮-盐性高血压大鼠脑脊液中的激肽释放酶

Cerebrospinal fluid kallikrein in spontaneously hypertensive and desoxycorticosterone acetate-salt hypertensive rats.

作者信息

Khan I M, Yamaji I, Miller D H, Margolius H S, Privitera P J

机构信息

Department of Pharmacology, Medical University of South Carolina, Charleston 29425.

出版信息

J Hypertens. 1993 Oct;11(10):1039-45. doi: 10.1097/00004872-199310000-00006.

DOI:10.1097/00004872-199310000-00006

PMID:8258667

Abstract

OBJECTIVE

To determine whether immunoreactive tissue kallikrein levels in cerebrospinal fluid (CSF) of spontaneously hypertensive rats (SHR) and desoxycorticosterone acetate (DOCA)--salt-treated hypertensive rats are elevated compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats.

DESIGN

The present study was designed to test the hypothesis that the activity of the brain tissue kallikrein-kinin system is enhanced in hypertensive states.

METHODS

Age-matched 18- to 19-week-old SHR and WKY rats, and Sprague-Dawley rats treated for 6 weeks either with 2 mg/kg per day DOCA subcutaneously and 0.9% saline in the drinking water, or with vehicle and tap water to drink, were studied. CSF was collected from a cannula inserted into the cisterna magna, and was frozen until the tissue kallikrein in the samples was measured by radioimmunoassay. Arterial pressure in the SHR and WKY rats was measured directly via a cannula inserted in the femoral artery or by tail-cuff plethysmography.

RESULTS

In adult 18- to 19-week-old SHR the CSF kallikrein concentration was higher than in WKY rats. The CSF flow rate in SHR was also higher than in WKY rats. The rate of appearance of kallikrein in the CSF of SHR was twice that in WKY rats. Moreover, CSF kininogenase activity in SHR was significantly higher than that in age-matched WKY rats. In DOCA--salt hypertensive rats the CSF kallikrein concentration was higher than in vehicle-treated control rats. Acute elevation of blood pressure with a 120-min intravenous phenylephrine infusion did not change the CSF kallikrein concentration in 50 rats compared with vehicle-treated control rats. This is the first study to quantitate immunoreactive tissue kallikrein in the CSF of rats and to show elevated levels of CSF kallikrein in hypertensive rats compared with normotensive rats.

CONCLUSION

The present data suggest that higher brain kallikrein activity in hypertensive rats may play a role in the development of elevated blood pressure.

摘要

目的

确定自发性高血压大鼠（SHR）和醋酸脱氧皮质酮（DOCA）-盐处理的高血压大鼠脑脊液（CSF）中免疫反应性组织激肽释放酶水平是否高于正常血压的Wistar-Kyoto（WKY）大鼠和Sprague-Dawley大鼠。

设计

本研究旨在检验高血压状态下脑组织激肽释放酶-激肽系统活性增强这一假说。

方法

对年龄匹配的18至19周龄SHR和WKY大鼠，以及皮下注射2mg/kg/天DOCA并饮用0.9%盐水6周的Sprague-Dawley大鼠，或注射溶媒并饮用自来水的Sprague-Dawley大鼠进行研究。通过插入枕大池的套管收集脑脊液，并冷冻保存，直至用放射免疫分析法测定样本中的组织激肽释放酶。通过插入股动脉的套管或尾袖体积描记法直接测量SHR和WKY大鼠的动脉血压。

结果

成年18至19周龄SHR的脑脊液激肽释放酶浓度高于WKY大鼠。SHR的脑脊液流速也高于WKY大鼠。SHR脑脊液中激肽释放酶的出现率是WKY大鼠的两倍。此外，SHR的脑脊液激肽原酶活性显著高于年龄匹配的WKY大鼠。与溶媒处理的对照大鼠相比，静脉注射去氧肾上腺素120分钟使血压急性升高，并未改变50只大鼠的脑脊液激肽释放酶浓度。这是第一项对大鼠脑脊液中免疫反应性组织激肽释放酶进行定量，并显示高血压大鼠脑脊液激肽释放酶水平高于正常血压大鼠的研究。