Cardioprotective effects of vasopeptidase inhibitors

In all cardiovascular disease, there is an imbalance between vasoconstrictor and vasodilator systems that favours vasoconstriction. Angiotensin-converting enzyme (ACE) inhibitors help to redress this imbalance. ACE inhibitors reduce angiotensin II and, by blocking the metabolism of bradykinin, ACE inhibitors upregulate nitric oxide and prostacycline. Neutral endopeptidase (NEP) is the major enzymatic pathway for the degradation of natriuretic peptides and adrenomedullin, and is a secondary enzymatic pathway for the degradation of kinins. Thus, inhibition of NEP increases levels of natriuretic and vasodilatory peptides. Vasopeptidase inhibitors (VPIs), by simultaneously inhibiting ACE and NEP, reduce vasocontriction and enhance vasodilation; thus, they improve local blood flow, and improve sodium and water excretion. In addition, they likely reduce growth, fibrosis, coagulability, adhesive molecule expression and monocyte adhesion, and inflammation in the vasculature and the heart. In clinical studies, they have proven to be very effective in treating hypertension. The major side effect of the drugs appears to be angioedema. Thus, VPIs are promising new drugs for the treatment of cardiovascular diseases.