Effects of captopril related to increased levels of prostacyclin and angiotensin-(1-7) in essential hypertension

Role of Mas receptor antagonist (A779) in renal hemodynamics in condition of blocked angiotensin II receptors in rats

“…Second, dual blockade of AT1R and AT2R increased RBF in male and female rats, but in male rats, there was a tendency to increase RBF/KW by A779 as compared with the vehicle. Chronic treatment with either ACE inhibitors or AT1R blockers increases plasma levels of Ang 1-7 (5-25-fold), Ang I and ACE2 activity (19,43). However, increase in Ang 1-7 leads to vasodilatory effects due to production of nitric oxide (NO) (28), potentiation of endogenous bradykinin (39) and binding Ang 1-7 to ACE that facilities the crosstalk between ACE and bradykinin B2 receptor (10,25,39).…”

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.…”

“…The germinal form, which is found exclusively in the testes, has 1 catalytic site and is involved in fertility. 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). [3][4][5][6] Blockade of Ang (1-7) by its specific receptor antagonist D-alanine 7 -Ang (1-7) reverses the blood pressure-lowering actions of ACE inhibitor lisinopril, 7 illustrating that the increased levels of Ang (1-7) account for a part of the antihypertensive actions of ACE inhibition.…”