The cardiac renin-angiotensin system. New insights from transgenic animal models

RESUMO

The renin-angiotensin system (RAS) was described for more than a century as a circulating hormone system regulating blood pressure and kidney function. The advent of molecular biology has added a novel aspect to the picture of the RAS namely the local production and action of components of the system in several organs including brain, adrenal gland, vascular wall, kidney, and heart. In particular the interest has focussed on the cardiac RAS since genetic as well as pharmacologic studies have suggested an important role of angiotensin in the heart Polymorphisms in the gene for angiotensin-converting enzyme were linked to the risk for cardiac diseases and inhibitors of this enzyme as well as angiotensin receptor antagonists turned out to be extremely effective drugs for the treatment fo heart failure. All components of the RAS are synthesized in the heart and, therefore, the local production of angiotensin II occurs in this organ. The interplay of this local system with the circulating RAS, mechanical stretch, and the sympathetic nervous system has recently been addressed by the generation of transgenic aninal models with targeted alterations in the expression of RAS components in the heart. The results are consistent with a pivotal function of the local RAS in the regulation of cardiac hypertrophy, remodelling, and fibrosis. However, there are still open questions concerning the autonomy of the RAS in these effects or its dependence on additional stimuli such as mechanical stretch or growth factors. This review summarizes the available evidence and discusses the remaining unsolved problems.