Ace inhibitors and cardiovascular regulation: the importance of autocrine and paracrine mechanisms

As demonstrated in a large number of clinical studies, angiotensin converting enzyme (ACE) inhibitors are of great value for the treatment of cardiovascular disorders. Although the clinical merits of these drugs are now well recognized, their mechanism of action is not yet completely understood. The beneficial effects of ACE inhibitors cannot simply be explained by a reduction in circulating angiotensin 11, leading to a decrease in vascular tone. In the last two decades, it has become clear that this class of drugs operates at different levels of cardiovascular regulation. Apart from their systemic effects, ACE inhibitors also interfere with biological processes within or between cells. These local mechanisms affect cellular biochemistry, biophysics and even gene expression and may in many ways contribute to the unique and complex pharmacologic profile of ACE inhibitors. In this thesis, the role of local or tissue hormones in the action of ACE inhibitors will be discussed.