Atrial natriuretic peptide mimetics and vasopeptidase inhibitors

There is now substantial evidence supporting a role of the natriuretic pept ides as a major defence mechanism against excess salt and water retention a nd high blood pressure. Because of this there has been considerable interes t in the therapeutic potential of the natriuretic peptide system. Several a pproaches have been explored including the use of native peptides, the deve lopment of natriuretic peptides mimetics and targetting of endogenous clear ance of natriuretic peptides. While ANP and BNP administration may be valua ble in some circumstances, however, the limitations of the use of peptides especially for long-term treatment are well apparent. In view of this, cons iderable effort has been devoted to the development of orally active agents to enhance endogenous natriuretic peptides through inhibition of breakdown by neutral endopeptidase. This research has now led to the vasopeptidase i nhibitors - dual inhibitors of both endopeptidase and angiotensin convertin g enzyme. These agents clearly provide a novel approach to enhance endogeno us natriuretic peptide function on a background of reduced angiotensin II a ctivity and may lead to an important advance in the treatment of hypertensi on and of conditions associated with overt salt and water overload. (C) 200 1 Elsevier Science BY All rights reserved.