Ramiprilat, the active metabolite of Ramipril, is a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Ramiprilat inhibits ACE with a Ki value of 7 pmol/l. It is both a slow- and tight-binding inhibitor; the mode of inhibition is fully competitive. Binding of ramiprilat to ACE proceeds by a two-step mechanism E + I in equilibrium EI in equilibrium EI in which the inhibitor rapidly binds to enzyme to form an initial enzyme-inhibitor complex, which then undergoes a slow isomerization[1]. The angiotensin-converting enzyme inhibitor ramiprilat (30 or 100 microM) has a protective effect on isolated cardiac myocytes exposed to hypoxia/reoxygenation and that this effect is most likely related to a local action of bradykinin on the cardiac myocyte via the activation of the kinin B2 receptor[2]. An acute infusion of ramiprilat significantly prevents the development of coronary endothelial dysfunction[3]. After an IV bolus of ramiprilat, the only changes in renal-impaired dogs were a 14 and 49% decrease in clearance of the free fraction of ramiprilat and free plasma concentration required to produce 50% of the maximal effect, respectively[4].
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