High level expression of human tissue kallikrein in the circulation induces hypotension in transgenic mice.

In order to create an animal model expressing a high level of tissue kallikrein in the circulation, the human tissue kallikrein gene was placed under the control of a mouse albumin enhancer and promoter to target its expression to liver. Three lines of transgenic mice carrying the human tissue kallikrein gene were established. The major site of human tissue kallikrein synthesis was identified in the liver of transgenic mice, and a high level of human tissue kallikrein was secreted into the mouse circulation. The systolic blood pressures of these transgenic mice are about 15-20 mmHg lower than that of the control mice. Administration of aprotinin, a potent tissue kallikrein inhibitor, restored normal blood pressure in these animals. These studies show that a high level of foreign tissue kallikrein in the circulation plays a role in blood pressure regulation.