High level of circulating human tissue kallikrein induces hypotension in a transgenic mouse model.
We established a unique transgenic mouse model in liver-targeted expression of human tissue kallikrein using a mouse albumin enhancer and promoter. Northern blot analysis and ELISA showed that human tissue kallikrein was predominantly expressed in the liver of transgenic mice and secreted into the circulation at a high level. The transcript was also detected in the kidney, pancreas, salivary gland and heart at a low level by reverse transcription-polymerase chain reaction followed by Southern blot analysis. Systolic blood pressures were measured by the tail-cuff method, all three independent transgenic mouse lines are hypotensive (84.6 +/- 1.0 mmHg, n = 17; 84.5 +/- 1.5 mmHg, n = 9; 83.1 +/- 0.8 mmHg, n = 13, P < 0.01) compared with the control mice (100.9 +/- 0.9 mmHg, n = 17). Administration of aprotinin, a potent tissue kallikrein inhibitor or Hoe 140, a bradykinin receptor antagonist, restored the blood pressure of transgenic mice but had no significant effect on control littermates. These studies show that over-production of tissue kallikrein in the circulation plays a role in blood pressure regulation.
Song
Q
Q
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425, USA.
Chao
J
J
Chao
L
L
D000818:Animals; D006801:Humans; D007022:Hypotension / Q000097:blood* / Q000209:etiology*; D007610:Kallikreins / Q000235:genetics / Q000493:pharmacokinetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D014018:Tissue Distribution
D012333:RNA, Messenger; D007610:Kallikreins