Present and future of ACE inhibition

Abstract

ACE Inhibitorsedited by P. D'Orleans-Juste and G.E. Plante, Birkhauser Verlag, 2001. Euro119 (hardback) (x + 184 pages) ISBN 376435982XToday, blockers of the renin–angiotensin system are standard therapy for essential hypertension and congestive heart failure, and represent an important step in the management of patients with diabetic and non-diabetic nephropathies. This success story started with the discovery and the clinical development of angiotensin-converting enzyme (ACE) inhibitors [1xRole of angiotensin and its inhibition in hypertension, ischemic heart disease, and heart failure. Gavras, H. and Brunner, H.R. Hypertension. 2001; 37: 342–345Crossref | PubMedSee all References[1] and has been amplified recently with the availability of specific angiotensin II AT1 receptor antagonists [2xAngiotensin II type 1 receptor blockers. Burnier, M. Circulation. 2001; 103: 904–912Crossref | PubMedSee all References[2]. There are several books on ACE inhibitors, but the most recent, edited by P. D'Orleans-Juste and G.E. Plante, deserves special attention because it covers several facets of ACE inhibitors that are not frequently discussed in such detail.The books starts with an interesting historical perspective written by Sir John Vane, Nobel laureate, who contributed personally to the understanding of the physiology of the ACE enzyme and participated in the early development of ACE inhibitors. His contribution describes the difficulty in developing a new therapeutic concept and the important role played by serendipity, chance and coincidences.M. Lamarre-Cliche and P. Larochelle present a very comprehensive analysis of all clinical trials that have been performed with ACE inhibitors in the various fields of hypertension, heart failure, post-myocardial infarction heart failure, acute myocardial infarction, diabetes, left ventricular hypertrophy, renal failure and patients with a high cardiovascular risk. This chapter underscores the tremendous clinical impact that ACE inhibitors have on the management of patients with cardiovascular diseases today.Another interesting chapter covers one important aspect of ACE inhibitors: their impact on the metabolism of kinins. The role of bradykinin in mediating the clinical effects of ACE inhibitors has always been a controversial issue. In this book, Adam et al. provides a critical analysis of the biochemistry and pharmacology of kinins in relation to the therapeutic effects and side-effects of ACE inhibitors. The interaction between ACE inhibitors and nitric oxide or the endothelin pathway, the role of the renin–angiotensin system on the central and peripheral autonomic nervous system, the effect of ACE inhibition on thirst and salt appetite, and the impact of ACE inhibitors on the microcirculation are some of the many basic and clinical facets of ACE inhibitors that are also discussed in this book.Future research directions in the field of ACE inhibition and the renin–angiotensin system are also proposed. Thus, M. Lajemi and A. Benetos reviewed numerous studies that have attempted to evaluate the role of genetic variants of the components of the renin–angiotensin system and their potential implications on cardiac and arterial phenotypes. Although there is always the secret hope that genotyping will enable identification of population subgroups that could benefit from early treatment with ACE inhibitors, this chapter confirms that there is still a long way to go until such hope is realised. Finally, the future therapeutic developments are discussed, and a new group of drugs that provide dual inhibition of ACE and neutral endopeptidase are reviewed. These new agents, at present under clinical investigation, offer the possibility of blocking the renin–angiotensin system and, simultaneously, potentiating the systemic and renal effects of atrial natriuretic peptides (ANPs). These drugs have an interesting therapeutic potential but the success of their development will depend on their tolerability profile [3xNovel angiotensin II inhibitors in cardiovascular medicine. Burnier, M. Expert Opin. Invest. Drugs. 2001; 10: 1957–1964Crossref | PubMed | Scopus (5)See all References[3].As a whole, this book represents a valuable working tool that covers several new facets of ACE inhibitors that might be of interest to clinicians treating patients with cardiovascular diseases, and to basic scientists working on the renin–angiotensin system.