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.