Abstract
Background Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN) to yield nitric oxide (NO) or a related species that activates soluble guanylate cyclase (sGC), resulting in cGMPmediated vasodilation [1]. Accordingly, established ALDH2 inhibitors attenuate GTN-induced vasorelaxation in vitro and in vivo. However, the ALDH2 hypothesis has not been reconciled with early studies demonstrating potent inhibition of the GTN response by diphenyleneiodonium (DPI) [2], a widely used inhibitor of flavoproteins, in particular NADPH oxidases. We addressed this issue and investigated the effects of DPI on GTN-induced relaxation of rat aortic rings and the function of purified ALDH2.
Highlights
Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN) to yield nitric oxide (NO) or a related species that activates soluble guanylate cyclase, resulting in cGMPmediated vasodilation [1]
DPI (0.3 μM) inhibited the high affinity component of aortic relaxation to GTN without affecting the response to NO, indicating that the drug interfered with GTN bioactivation
DPI (10 μM) caused a pronounced right-ward shift of the GTN concentration response (Figure 1B), indicating that the drug acts in a GTN-competitive manner
Summary
From 6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications Erfurt, Germany. From 6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications Erfurt, Germany. 28-30 June 2013
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