Chemistry of the inhibitors of the renin-angiotensin system.

The enzyme renin splits a single peptide bond in the plasma glycoprotein angiotensinogen liberating the biologically inactive decapeptide angiotensin I (ANG I). A second enzyme, angiotensin converting enzyme (CE), releases the strong vasoconstricting octapeptide ANG II via degradation of a C-terminal dipeptide. The effect of this compound on blood pressure can be attenuated by interference with the enzyme-controlled peptide cascade of the renin-angiotensin system (RAS). This is accomplished by inhibition of renin and CE, respectively. Orally active CE inhibitors are valuable drugs in the treatment of renal and essential hypertension and of heart failure. Strong inhibitors of renin have also been synthesized, however, peptide moieties which have still to be present in these compounds impede oral absorption. Finally, antagonistic analogues of ANG II are able to block its effect on the receptor level. Their application is limited by the still existing partial agonistic activity.