Activation of the Renin-Angiotensin System in Heart Failure and Hypertrophy--Studies in Human Hearts and Transgenic Rats

Numerous in vitro studies have demonstrated that angiotensin II has distinctive cellular effects in the cardiovascular system, independent from its effects on blood pressure. These have led to the hypothesis that activation of the angiotensin system in the heart could be of functional relevance for the adaptive processes in several cardiovascular disorders, such as cardiac hypertrophy and heart failure. This concept has been supported by clinical studies showing the beneficial effects of blockers of the system such as angiotensin converting enzyme (ACE) inhibitors in these circumstances. In order to study the regulation of gene expression of renin angiotensin system components in cardiac disorders we have performed two studies. First, we investigated the gene expression of ACE in human heart failure. Results showed that the enzyme is activated locally in this condition, supporting previous studies in animals. Second, in a different approach, we asked whether the selective activation of the renin angiotensin system in the hearts of transgenic rats expressing an additional renin gene leads to the development of pathological changes in the cardiovascular system. The results of this study demonstrated that the transgenic animals developed cardiac hypertrophy and heart failure independent of the increase in blood pressure seen in these rats. Taken together, these studies provide further evidence for the functional role of local angiotensin systems in the heart.