Abstract 245: Prevention of Glyceryl Trinitrate Tolerance by Flavonoids
Background and propose: The anti-ischemic effects of glyceryl trinitrate (GTN) are rapidly blunted after continuous application. This phenomenon of GTN tolerance may be the result of an increased oxidative stress and/or a reduced bioactivation of GTN by the enzyme aldehyde dehydrogenase (ALDH). The polyphenolic compounds flavonoids are reported to potentiate vascular relaxation and inhibit oxidation. Therefore, in the present study, we assessed the hypothesis that flavonoids can prevent GTN tolerance. Whether or not this effect of flavonoids is related to their anti-oxidative property or modulation of the activity of ALDH was also examined.
Experimental approach: Isolated rat aortic rings were incubated with modified Krebs-Henseleit solution containing GTN (30 μM) in organ chamber at 37°C for 1 hour to induce tolerance. Flavonoids (10 μM of apigenin, luteolin, kaempferol, quercetin, genistin, genistein, narigenin, catechin or epicatechin) or the vehicle (1 mM dimethyl sulfoxide) were added to the aortic rings 30 minutes before GTN treatment. Those rings without incubation with GTN were served as the respective control groups. After removing the treatment solution, rings were contracted with phenylephrine (1 μM) followed by cumulative addition of GTN (0.1 nM to 30 μM). GTN-induced relaxation was calculated as change in isometric tension of aortic rings from the contraction induced by phenylephrine. Vascular ALDH activity was assayed by spectrophotometry as the rate of NAD+ consumption.
Key results: GTN-induced relaxation in rat aortic rings was reduced by prior incubation with GTN; this reduction was prevented by apigenin (10 μM), which did not affect the relaxations in the group without prior treatment with GTN. Apigenin (10 μM) also increased the vascular ALDH activity which was reduced by prior GTN incubation.
Conclusion: Apigenin appears to have the potential to prevent the development of GTN tolerance, likely by restoring the bioactivation of GTN by ALDH.
Author Disclosures: L. Zhang: None. S.W. Leung: None. R.Y. Man: None.
- © 2015 by American Heart Association, Inc.