CEREBROSPINAL-FLUID KALLIKREIN IN SPONTANEOUSLY HYPERTENSIVE AND DEOXYCORTICOSTERONE ACETATE SALT HYPERTENSIVE RATS

Objective: To determine whether immunoreactive tissue kallikrein level s in cerebrospinal fluid (CSF) of spontaneously hypertensive rats (SHR ) and desoxycorticosterone acetate (DOCA)-salt-treated hypertensive ra ts are elevated compared with normotensive Wistar-Kyoto (WKY) and Spra gue-Dawley rats. Design: The present study was designed to test the hy pothesis that the activity of the brain tissue kallikrein-kinin system is enhanced in hypertensive states. Methods: Age-matched 18- to 19-we ek-old SHR and WKY rats, and Sprague-Dawley rats treated for 6 weeks e ither 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 measu red directly via a cannula inserted in the femoral artery or by tail-c uff plethysmography. Results: In adult 18- to 19-week-old SHR the CSF kallikrein concentration was higher than in WKY rats. The CSF flow rat e in SHR was also higher than in WKY rats. The rate of appearance of k allikrein 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 c oncentration was higher than in vehicle-treated control rats. Acute el evation of blood pressure with a 120-min intravenous phenylephrine inf usion did not change the CSF kallikrein concentration in 50 rats compa red with vehicle-treated control rats. This is the first study to quan titate 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 br ain kallikrein activity in hypertensive rats may play a role in the de velopment of elevated blood pressure.