High level of circulating human tissue kallikrein induces hypotension in a transgenic mouse model.
Clin Exp Hypertens
; 18(8): 975-93, 1996 Nov.
Article
em En
| MEDLINE
| ID: mdl-8922341
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Calicreínas
/
Hipotensão
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Clin Exp Hypertens
Ano de publicação:
1996
Tipo de documento:
Article