INHIBITION OF RENIN-ANGIOTENSIN SYSTEM: It is now possible to effectively block the renin-angiotensin system at several steps by orally active inhibitors. Blockade of renin, the angiotensin coverting enzyme (ACE) or the angiotensin II (Ang II) type 1 (AT1) receptor leads to different hormonal changes. All three modes of blockade reduce aldosterone and all cause a reactive rise in plasma renin due to removal of angiotensin II tonic inhibition on renal renin release. ASSOCIATED CHANGES IN ANG I AND ANG II: AT1 blockade by losartan is followed by rises in plasma Ang I and Ang II; ACE inhibitors are associated with an increase in plasma Ang I but a fall in Ang II, whereas both plasma Ang I and Ang II fall with renin inhibition. DIFFERENCES IN MODE OF INHIBITION: Potential differences between the mode of blockade of the renin-angiotensin system include differences in the bioavailability of compounds, the effect of ACE on other peptide substrates, particularly bradykinin, the possibility of other actions or unknown substrates for renin and the presence of unblocked AT2 angiotensin receptors in the presence of high levels of Ang II. Whether these will result in clinically important differences remains to be determined.