Effect of vitamin C on forearm blood flow and glucose metabolism in essential hypertension

In 9 patients with essential hypertension, we tested whether a high-dose (1 2 mg.min(-1)) vitamin C infusion into the brachial artery, by improving end othelium-dependent vasodilatation, would also attenuate the insulin resista nce of deep forearm tissues. We measured the effect of vitamin C on acetylc holine (Ach)-induced vasodilatation and on forearm glucose uptake during sy stemic hyperinsulinemia; in all studies, the contralateral forearm served a s the control. Intrabrachial Ach infusion produced a stable increase in for earm blood flow, from 2.6 +/- 0.3 to 10.6 +/- 2.1 mL.min(-1).dL(-1); when v itamin 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, bloo d flow in both the infused and control forearms did not significantly chang e from baseline values (+10 <plus/minus> 16% and +2 +/- 11%, respectively). In contrast, when vitamin C was added, blood flow in the infused forearm i ncreased significantly (to 3.7 +/- 0.7 mL.min(-1).dL(-1); P < 0.02 vs 2.8 < plus/minus> 0.6 mL.min(-1).dL(-1) in the control forearm). Insulin stimulat ed whole-body glucose disposal to 20 +/- 2 mu mol.min(-1) kg(-1), compatibl e with the presence of marked insulin resistance. Forearm glucose uptake wa s similarly stimulated after 80 minutes of insulin infusion (to 2.11 +/- 0. 42 and 2.06 +/- 0.43 mu mol.min(-1)dL(-1), infused and control, respectivel y). When intrabrachial vitamin C was added, no difference in glucose uptake was observed between the 2 forearms (infused, 2.37 +/- 0.44 mu mol.min(-1) .dL(-1) and control, 2.36 +/- 0.53 mu mol.min(-1).dL(-1)). Forearm O-2 upta ke at baseline was also similar in the 2 forearms (infused, 9.7 +/- 0.7 mu mol.min(-1).dL(-1) and control, 9.6 +/- 1.1 mu mol.min(-1).dL(-1)) and was not changed by either insulin or vitamin C. We conclude that in the deep fo rearm tissues of patients with essential hypertension and insulin resistanc e, an acute improvement in endothelial function, obtained with pharmacologi cal doses of vitamin C, restores insulin-mediated vasodilatation but does n ot improve insulin-mediated. glucose uptake. Thus, the endothelial dysfunct ion of essential hypertension is unlikely to be responsible for their metab olic insulin resistance.