NEW HORMONAL BLOCKADE STRATEGIES IN CARDIOVASCULAR-DISEASE

The circulation is controlled by overlapping haemodynamic, structural and neurohumoral mechanisms. Many hormonal vasoactive substances, most ly derived from endothelial cells, are also growth regulators. Althoug h neurohormonal systems are involved in normal physiological compensat ory responses they often become maladaptive in conditions such as cong estive heart failure. The success of blocking the renin angiotensin sy stem by angiotensin converting enzyme (ACE) inhibitors has led to effo rts to block other hormonal systems. Neutral endopeptidase (NEP), the major enzymatic pathway for degradation of natriuretic peptides, has a similar catalytic site to ACE. This has led to compounds that simulta neously inhibit both enzymes. Such dual ACE/NEP inhibitors show promis e in experimental hypertension and heart failure. Similar dual NEP/ECE (endothelin converting enzyme) inhibitors are becoming available. The hormone vasopressin has dual actions on the vasculature and the kidne y via specific membrane receptors. Specific orally active vasopressin receptor antagonists have been developed and their therapeutic potenti al in hypertension, heart failure and oedematous states are being expl ored.