Renin inhibitors as possible antihypertensive agents

The blockade of the renin-angiotensin system by inhibition of angiotensin-converting enzyme has become an established principle in the treatment of hypertension. This has stimulated interest in the inhibition of renin, the enzyme which catalyzes the first and rate-limiting step in the formation of angiotensin II. During recent years, considerable progress has been made in the development of renin inhibitors. Several potent and selective compounds have been synthesized and studied in vitro and in vivo. In experimental animals with a stimulated renin-angiotensin system the haemodynamic effects of renin inhibitors have been shown to be identical to those of angiotensin-converting enzyme inhibitors. The two classes of agents also have similar antihypertensive effects in various forms of experimental renal hypertension. However, it is not clear whether then efficacy will be comparable in patients with essential hypertension. The main shortcoming of the currently available renin inhibitors is their low bioavailability after oral administration and their short duration of action. The improvement of these pharmacokinetic properties is the main challenge for future research in this area.