Because of the species-specific interaction of the human renin and angiotensinogen, the testing of human specific drugs interfering with the renin-angiotensin system (RAS) is restricted to primates. In the present paper we report the development of transgenic rat lines carrying either the human renin or angiotensinogen gene. Both human genes are expressed in various tissues and human prorenin, renin and angiotensinogen could be detected in the plasma of the transgenic animals in significant amounts. Because of the species-specificity of the human RAS no enhanced blood pressure or angiotensin II concentration was found in transgenic rats. However, infusion of human renin into transgenic rats carrying the human angiotensinogen gene but not into negative littermates resulted in an increase of both plasma angiotensin II concentration and blood pressure which could be completely abolished by pretreatment of the animals with human renin specific inhibitor RO 425892. In contrast, rat renin infusion also leads to an increase of both parameters but could not be antagonized by RO 425892, Therefore, such transgenic rats carrying either the human renin or angiotensinogen gene will offer the opportunity to study human specific enzyme kinetics and to test human RAS specific drugs in vivo in a non-primate model.
|Number of pages||3|
|Journal||Nieren- und Hochdruckkrankheiten|
|Publication status||Published - Nov 1992|