Modulation of angiotensin‐converting enzyme by nitric oxide

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Abstract
The aim of the present study was to determine the effect of nitric oxide (NO) on angiotensin‐converting enzyme (ACE) activity. A biochemical study was performed in order to analyse the effect of the NO‐donors, SIN‐1 and diethylamine/NO (DEA/NO), and of an aqueous solution of nitric oxide on the ACE activity in plasma from 3‐month old male Sprague‐Dawley rats and on ACE purified from rabbit lung. SIN‐1 significantly inhibited the activity of both enzymes in a concentration‐dependent way between 1 and 100 μM. DEA/NO inhibited the activity of purified ACE from 0.1 μM to 10 μM and plasma ACE, with a lower potency, between 1 and 100 μM. An aqueous solution of NO (100 and 150 μM) also inhibited significantly the activity of both enzymes. Lineweaver‐Burk plots indicated an apparent competitive inhibition of Hip‐His‐Leu hydrolysis by NO‐donors. Modulation of ACE activity by NO was also assessed in the rat carotid artery by comparing contractions elicited by angiotensin I (AI) and AII. Concentration‐response curves to both peptides were performed in arteries with endothelium in the presence of the guanylyl cyclase inhibitor, ODQ (10 μM), and the inhibitor of NO formation, L‐NAME (0.1 mM). NO, which is still released from endothelium in the presence of 10 μM ODQ, elicited a significant inhibition of AI contractions at low concentrations (1 and 5 nM). In the absence of endothelium, 1 μM SIN‐1 plus 10 μM ODQ, as well as 10 μM DEA/NO plus 10 μM ODQ induced a significant inhibition on AI‐induced contractions at 1 and 5 nM and at 1–100 nM, respectively. In conclusion, we demonstrated that (i) NO and NO‐releasing compounds inhibit ACE activity in a concentration‐dependent and competitive way and that (ii) NO release from endothelium physiologically reduces conversion of AI to AII.

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