Vitamin C Deficiency Exerts Paradoxical Cardiovascular Effects in Osteogenic Disorder Shionogi (ODS) Rats

Abstract

Vitamin C is considered to be a very efficient water-soluble antioxidant, for which several new cardiovascular properties were recently described. The aim of this study was to determine in vivo the effects of a severe depletion of vitamin C on cardiac and vascular variables and reperfusion arrhythmias. For this purpose, we used a mutant strain of Wistar rats, osteogenic disorder Shionogi (ODS). After 15 d of consuming a vitamin C-deficient diet, ODS rats had a 90% decrease in plasma and tissue levels of ascorbate compared with ODS vitamin C-supplemented rats and normal Wistar rats. However, plasma antioxidant capacity, proteins, alpha-tocopherol, urate, catecholamines, lipids, and nitrate were not influenced by the vitamin C deficiency in ODS rats. Moreover, there was no difference between ODS vitamin C-deficient and -supplemented rats in heart rate and arterial pressure. After 5 min of an in vivo regional myocardial ischemia, various severe arrhythmias were observed, but their intensities were not modified by vitamin C in vitamin C-deficient ODS rats. The vascular reactivity, measured in vitro on thoracic arteries, was not altered by ascorbate deficiency in ODS rats. These unexpected results suggest that unidentified compensatory mechanisms play a role in maintaining normal cardiac function and vascular reactivity in vitamin C-deficient rats.

Nitroso-Redox Status and Vascular Function in Marginal and Severe Ascorbate Deficiency

“…The main mechanisms proposed include stimulation of nitric oxide synthase (NOS) activity by modulation of cofactor requirements, sparing of intracellular thiols, and release of NO from circulating/tissue storage forms. Irrespective of mechanism, these results are inconsistent with the reported lack of endothelial dysfunction in ODS (Osteogenic, Disorder Shionogi) rats (45), a strain derived from the Wistar rat that carries a missense mutation of L-gulonolactone oxidase, rendering these animals incapable of synthesizing ascorbate (23,31). Interestingly, Gulo -/-mutant mice, a genetically engineered mouse lacking the same enzyme, present with aortic wall damage on withdrawal of ascorbate supplementation (27), consistent with the association between low ascorbate levels and cardiovascular disease.…”

“…If high doses of ascorbate augment cardiac function, confer cardioprotection, and enhance endotheliumdependent vasorelaxation (3), then its depletion might be expected to cause the opposite. However, Vergely et al (45) had reported that ODS rats reveal improved vascular reactivity compared to Wistar controls. We here confirm and extend those results to show that endothelial reactivity is enhanced regardless of ascorbate supplementation status and associated with an increase in basal and stimulated endothelial NO production without changes in sensitivity of the NO receptor, soluble guanylyl cyclase, or downstream processes of vasorelaxation.…”

Poor vitamin C status is associated with increased carotid intima-media thickness, decreased microvascular function, and delayed myocardial repolarization in young patients with type 1 diabetes

“…B: Association of the maximum response to Ach with plasma vitamin C in 59 children and adolescents with type 1 diabetes (P = 0.005, r = 0.41). biosynthesis, showed no difference in heart rate, arterial blood pressure, and occurrence or persistency of rhythm abnormalities in relation to vitamin C supplementation (29). The reason for this discrepancy is not clear.…”

Postnatal overfeeding in rats leads to moderate overweight and to cardiometabolic and oxidative alterations in adulthood

“…Unlike humans, rats synthetize their own vitamin C in the liver, but they can also ingest it in their food. However, intestinal transporters of ascorbate or dehydroascorbate are not very abundant in rodents except in gulunolactone oxidase-deficient strains [39,40] and the composition of the standard diet we have used in our study does not mention the presence of vitamin C. Therefore, the decrease in vitamin C could be related to a higher depletion of this hydro-soluble antioxidant vitamin due to increased circulating oxidative stress, evidenced by higher peroxidation markers. However, we cannot exclude the possibility of lower hepatic synthesis of vitamin C. This increase in oxidative stress cannot be explained by increased NADPH oxidase activity in vessels or tissues, since in our study it was not modified in OF aortas or hearts.…”