The effect of vitamin C on nitroglycerin‐mediated vasodilation in individuals with and without the aldehyde dehydrogenase 2 polymorphism

• Published in: British journal of clinical pharmacology Vol. 89; no. 9; pp. 2767 - 2774
• Main Authors: He, Jerry D., Parker, John D.
• Format: Journal Article
• Language: English
• Published: England 01.09.2023
• Subjects: aldehyde dehydrogenase 2; cardiovascular pharmacology; nitroglycerin bioactivation; vitamin C; aldehyde dehydrogenase 2; nitroglycerin bioactivation; cardiovascular pharmacology; vitamin C
• DOI: 10.1111/bcp.15755
• ISSN: 0306-5251; 1365-2125

Aims To mediate its pharmacodynamic effects, glyceryl trinitrate (GTN) requires bioactivation, by which it releases nitric oxide or a nitric oxide moiety. The exact mechanism of GTN bioactivation remains uncertain. Mitochondrial aldehyde dehydrogenase (ALDH‐2) has been proposed as the primary enzyme responsible for this bioactivation process. Evidence for the importance of ALDH‐2 in GTN bioactivation has been inconsistent, particularly in human models. An alternative hypothesis suggests that decreased ALDH‐2 activity leads to accumulation of reactive cytotoxic aldehydes, which either inhibit the vasoactive product(s) of GTN or impair other enzymatic pathways involved in the bioactivation of GTN. We investigated the effect of supplemental vitamin C on vascular responses to GTN in healthy volunteers of East Asian descent, of whom 12 with and 12 without the ALDH‐2 polymorphism participated. Methods Subjects underwent 2 sequential brachial artery infusions of GTN at rates of 5, 11 and 22 nmol/min, separated by a 30‐min washout period. The GTN infusions were carried out in the presence and absence of vitamin C using a randomized, crossover design. Venous occlusion plethysmography was used to measure forearm blood flow responses to GTN. Results Compared to subjects with functional ALDH‐2, the variant group exhibited blunted hemodynamic responses to intra‐arterial GTN infusions, although this reduction in response was not statically significant. Contrary to our hypothesis, vitamin C had an inhibitory effect on GTN mediated vasodilation as compared to GTN during saline in both groups. Conclusion We conclude that vitamin C did not augment the acute vascular response to GTN in those with the ALDH‐2 polymorphism.