[Renin inhibition by peptides and pseudo-peptides]

The only known action of renin is the hydrolysis of angiotensinogen into angiotensin I. Renin is synthesized as an inactive precursor, preprorenin. The processing of prorenin into active renin occurs after the clivage of a profragment, just after a dibasic pair of amino-acids. Renin, like other aspartyl proteases, hydrolyses its substrate in its active center where two aspartyl residues are involved in the catalytic mechanism. The strong species specificity of renin lies in its interaction with its substrate through subsites which can be modelized by computer graphics. There is much promise in the inhibition of the renin angiotensin system at the level of the renin-angiotensinogen reaction. Potent and specific pepstatin-derived inhibitors have been synthesized which are able to inhibit primate renin in vitro and in vivo with a long duration of action. Other transition state analogs inhibitors have been administered parenterally in humans and similar results have been obtained. The concept of the treatment of hypertension by an anti-renin drug is emerging a reality. However, it remains to find an orally active and non toxic compound which will compare well with the present converting enzyme inhibitors.