Genetic targeting of the brain renin-angiotensin system in transgenic rats: impact on stress-induced renin release.

Abstract

The advance of genetic technologies to permit tissue-specific targeted gene manipulation allowed the development of transgenic models with alterations of the renin-angiotensin (RAS) solely in the brain. We have used such methodology to develop a transgenic rat with a brain specific alteration of the RAS [TGR(ASrAOGEN)], in order to elucidate a causative role for the brain RAS and its relevance in different pathophysiological processes. The TGR(ASrAOGEN) rats have decreased levels of angiotensinogen (AOGEN) throughout the brain because of an antisense inhibition of the astroglial AOGEN synthesis. In this review we aimed at summarizing the experience obtained from utilizing the TGR(ASrAOGEN) rat model to study the brain RAS and present novel results providing evidence for the involvement of this system in stress-induced renin release.