Active fragments of angiotensin II: Enzymatic pathways of synthesis and biological effects

Angiotensin (Ang) II is not the only active peptide of the renin-angiotensin system. Several of its degradation products including Ang Ill (obtained by deletion of the N terminal amino acid), Ang IV (obtained by deletion of the two N terminal amino acids) and Ang II(1-7) (obtained by deletion of the C terminal amino acid) also possess biological functions, These peptides are formed via the activity of several enzymes, aminopeptidase A for Ang Ill, aminopeptidases la and N for Ang IV, prolylendopeptidase and carboxypeptidases for Ang II(1-7). Ang Ill possesses most of the properties of Ang II and shares the same receptors. This peptide is particularly important in brain and pituitary physiology and plays a major role in the secretion of arginine vasopressin. Ang IV possesses its own receptors distinct from AT(1) and AT(2). Some of its effects (for example, stimulation of the synthesis of the type 1 inhibitor of plasminogen activator by endothelial cells) were previously attributed to Ang II. Others are opposed to Ang II effects (renal and cerebral vasodilation), Its role in vascular, renal and cerebral physiology remains to be determined. Ang II(1-7) exhibits direct and indirect effects, the latter resulting from Ang II(1-7)-dependent formation of nitric oxide and vasodilatory prostaglandins. Ang II(1-7) recognizes both specific receptors and AT(1) receptors as shown by the partial antagonistic properties of losartan, Ang II(1-7) plays essentially a role in the control of the hydroelectrolytic balance by increasing glomerular filtration rate, urinary output and sodium excretion rate.