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Vascular Biology |
Effect of Vitamin C on Forearm Blood Flow and Glucose Metabolism in Essential Hypertension
From the Department of Internal Medicine, University of Pisa (A.N., A.M.S., E.T., S.C., S.T., E.F.), Pisa, and the Metabolism Unit of the CNR Institute of Clinical Physiology (G.S., A.P.), Pisa, Italy.
Correspondence to Dr Andrea Natali, Dipartimento di Medicina Interna, Università degli Studi di Pisa, Via Roma 67, 56100 Pisa, Italy. E-mail anatali{at}ifc.pi.cnr.it
Abstract—In 9 patients with essential hypertension, we tested whether a high-dose (12 mg · min-1) vitamin C infusion into the brachial artery, by improving endothelium-dependent vasodilatation, would also attenuate the insulin resistance of deep forearm tissues. We measured the effect of vitamin C on acetylcholine (Ach)-induced vasodilatation and on forearm glucose uptake during systemic hyperinsulinemia; in all studies, the contralateral forearm served as the control. Intrabrachial Ach infusion produced a stable increase in forearm blood flow, from 2.6±0.3 to 10.6±2.1 mL · min-1 · dL-1; when vitamin C was added, a further rise in forearm blood flow (to 13.4 mL · min-1 · dL-1; P<0.03 vs Ach alone) was observed. In response to insulin, blood flow in both the infused and control forearms did not significantly change from baseline values (+10±16% and +2±11%, respectively). In contrast, when vitamin C was added, blood flow in the infused forearm increased significantly (to 3.7±0.7 mL · min-1 · dL-1; P<0.02 vs 2.8±0.6 mL · min-1 · dL-1 in the control forearm). Insulin stimulated whole-body glucose disposal to 20±2 µmol · min-1 · kg-1, compatible with the presence of marked insulin resistance. Forearm glucose uptake was similarly stimulated after 80 minutes of insulin infusion (to 2.11±0.42 and 2.06±0.43 µmol · min-1 · dL-1, infused and control, respectively). When intrabrachial vitamin C was added, no difference in glucose uptake was observed between the 2 forearms (infused, 2.37±0.44 µmol · min-1 · dL-1and control, 2.36±0.53 µmol · min-1 · dL-1). Forearm O2 uptake at baseline was also similar in the 2 forearms (infused, 9.7±0.7 µmol · min-1 · dL-1 and control, 9.6±1.1 µmol · min-1 · dL-1) and was not changed by either insulin or vitamin C. We conclude that in the deep forearm tissues of patients with essential hypertension and insulin resistance, an acute improvement in endothelial function, obtained with pharmacological doses of vitamin C, restores insulin-mediated vasodilatation but does not improve insulin-mediated glucose uptake. Thus, the endothelial dysfunction of essential hypertension is unlikely to be responsible for their metabolic insulin resistance.
Key Words: essential hypertension • insulin resistance • vitamin C • forearm
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