Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus.

Abstract

Endothelium-dependent vasodilation is impaired in humans with diabetes mellitus. Inactivation of endotheliumderived nitric oxide by oxygen-derived free radicals contributes to abnormal vascular reactivity in experimental models of diabetes. To determine whether this observation is relevant to humans, we tested the hypothesis that the antioxidant, vitamin C, could improve endothelium-dependent vasodilation in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus. We studied 10 diabetic subjects and 10 age-matched, nondiabetic control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intraarterial infusion of methacholine (0.3-10 g/min). Endothelium-independent vasodilation was measured by intraarterial infusion of nitroprusside (0.3-10 g/min) and verapamil (10-300 g/min). Forearm blood flow dose-response curves were determined for each drug before and during concomitant intraarterial administration of vitamin C (24 mg/min). In diabetic subjects, endothelium-dependent vasodilation to methacholine was augmented by simultaneous infusion of vitamin C ( P ϭ 0.002); in contrast, endothelium-independent vasodilation to nitroprusside and to verapamil were not affected by concomitant infusion of vitamin C ( P ϭ 0.9 and P ϭ 0.4, respectively). In nondiabetic subjects, vitamin C administration did not alter endothelium-dependent vasodilation ( P ϭ 0.8). We conclude that endothelial dysfunction in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus can be improved by administration of the antioxidant, vitamin C. These findings support the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes. ( J. Clin. Invest. 1996. 97:22-28.) Key words: ascorbate • antioxidants • free radicals • endothelium-derived relaxing factor • vascular

Circulating concentrations of asymmetrical dimethyl- L -arginine are increased in women with previous gestational diabetes

“…It is known that insulin resistance is associated with endothelial dysfunction [30], where increased oxidative stress is also detectable [31]. Under normal conditions, the formation of reactive oxygen species is kept under tight control by the capacity of the endogenous antioxidant defence system [32].…”

Superoxide as a Messenger of Endothelial Function

“…Knapp and Klann (2000) had reported an • O 2 -stimulated PKC activation via thiol oxidation. On the other hand studies on the multicomponent phagocyte 7-9 and endothelial NAD(P)H oxidase (Fontayne et al, 2002, Guzik et al 2002 Treatment of vessels from diabetic animals with SOD improved endothelium-dependent relaxations (Tesfamariam et al, 1992) and the use of vitamin C in patients with non-insulin (NIDDM) and insulin-dependent diabetes mellitus (IDDM), increased the endotheliumdependent vasodilation in the forearm circulation (Ting et al, 1996;Timimi et al, 1998). antioxidant.…”

Endothelial dysfunction and hypertension in aging

“…Endothelial function is restored by appropriate interventions, including pharmacological therapy, such as renin-angiotensin system inhibitors and statins, supplementation therapy and lifestyle modifications. 11,[31][32][33][34][35] ASSESSMENT OF ENDOTHELIAL FUNCTION In experimental studies, methods for assessment of endothelial function have been established by using a ring experiment protocol, endothelial functional alteration in expression of transcriptional factors and genes and genetic ablation of endothelial NO synthase (eNOS) in animal models. 36,37 It is clinically important to estimate the degree of endothelial dysfunction.…”