Metabolism of Angiotensin-(1–7) by Angiotensin-Converting Enzyme

Abstract

Abstract-Anglotensm converting enzyme (ACE) mhlbltors augment clrculatmg levels of the vasodllator peptlde anglotensm-(l-7)

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

“…ANG-(1-7) is subsequently metabolized into an inactive fragment, ANG-(1-5), by ACE [164][165][166]. The half-life of ANG-(1-7) is several seconds, and ACE inhibitors, which inhibit the metabolism of ANG-(1-7) into ANG-(1-5), increase the half-life of ANG-(1-7) [167].…”

Blood pressure and renal hemodynamic effects of angiotensin fragments

“…Ang-(1-7) has a shorter half-life than Ang II; it can be catabolized by ACE into the biologically inactive pentapeptide, Ang-(1-5), or by aminopeptidases into inactive fragments. 100,137 The G-protein-coupled Mas receptor was reported to mediate some of the effects of Ang-(1-7). 138 Alternatively, other effects of Ang-(1-7) appeared to be mediated by AT 1 and AT 2 receptors as they were inhibited by the AT 1 and AT 2 receptor-selective antagonists (Figure 2), 139 although radioligand binding assays suggested that these were low-affinity interactions.…”

Does the Angiotensin-Converting Enzyme (ACE)/ACE2 Balance Contribute to the Fate of Angiotensin Peptides in Programmed Hypertension?

“…Although ACE2 was first shown to hydrolyze Ang I to release Ang (1-9) with subsequent hydrolysis by ACE to Ang (1-7) in cardiomyocytes, the kinetic data by Vickers et al 11 with recombinant ACE2 revealed a relatively low catalytic constant (kcat) for Ang (1-9) formation. In contrast, the hydrolysis of Ang II to Ang (1-7) by ACE2 exhibited a very high catalytic efficiency (kcat/Km), Ϸ400-fold greater than that for Ang I to Ang (1)(2)(3)(4)(5)(6)(7)(8)(9). In this scheme, the formation of the vasodilator peptide Ang (1-7) occurs at the expense of the vasoconstrictor hormone Ang II.…”

“…Indeed, ACE inhibitors attenuate Ang II formation and augment the levels of the heptapeptide Ang (1-7), a peptide that counterbalances the actions of Ang II on blood pressure and cellular growth through a unique receptor system. Ang II mediates the majority of its actions at the Ang II type 1 (AT 1 ) receptor, including the stimulation of vasoconstriction, sodium retention, cellular growth, and oxidative stress, whereas recent studies show that Ang (1-7) at the AT [1][2][3][4][5][6][7] or mas receptor and Ang II via the AT 2 receptor subtype counterregulate the actions of Ang II at the AT 1 receptor.…”

“…Recently, it has been shown that ACE hydrolyzes Ang (1-7) to Ang (1)(2)(3)(4)(5), thus facilitating the breakdown of Ang (1-7). 1,2 Under conditions of ACE inhibition, not only is there an increase in the substrate Ang I, which can be converted to Ang (1-7) through the action of endopeptidases such as neprilysin and prolylendopeptidase, but there is also prevention of the breakdown of Ang (1-7). Acting at multiple sites in the processing scheme, ACE inhibition results in increased plasma, tissue, and urine levels of Ang (1-7).…”