From the Department of Medicine, State University of New York, and
Millard Fillmore Hospital, Buffalo, NY.
Correspondence to Bong Hee Sung, PhD, Department of Medicine, Millard Fillmore Hospital, 3 Gates Cir, Buffalo, NY 14209. E-mail bsung{at}MFHS.edu
AbstractRecently we have reported
that insulin attenuates norepinephrine (NE)-induced
vasoconstriction via a cyclic GMPNO synthase pathway. Because
hypercholesterolemia has been associated with
abnormal endothelial function, we investigated whether
insulin-mediated vasodilation is impaired in
hypercholesterolemia. To assess vasoreactivity,
NE (12.5, 25, 50, and 100 ng/min), NE (100 ng/min) combined with
insulin (8, 16, 24, and 32 µU/min), and NE (100 ng/min) combined with
sodium nitroprusside (0.01, 0.1, 1, 10, and 100 ng/min) were infused
into dorsal hand veins. Changes in venous diameter were measured by
ultrasonography, using a 7.5-MHz transducer. Twenty-two healthy,
normotensive hypercholesterolemic subjects (HC; mean
total cholesterol 6.93 mmol/L, HDL 1.45 mmol/L,
LDL 4.81 mmol/L) and 18 age-matched normal control subjects (NC;
mean total cholesterol 4.81 mmol/L, HDL 1.16
mmol/L, LDL 3.18 mmol/L) were studied. All HC had normal glucose
tolerance test results. Baseline vein diameters were similar between
groups, and the vasoconstrictor response to NE was not significantly
different between HC and NC. Insulin significantly attenuated
NE-induced vasoconstriction in NC but not in HC
(P<0.01). Both groups were able to venodilate with
sodium nitroprusside. To investigate the effects of
cholesterol reduction on vascular reactivity,
venoreactivity studies were repeated in 12 HC after treatment with 20
to 40 mg/d lovastatin for 6 weeks. There were no
significant venoreactivity changes with the treatment. Plasma LDL
cholesterol concentration was inversely correlated to
venodilator effect of insulin (r=-0.42,
P<0.02). In conclusion, insulin-mediated vasodilation
is impaired in patients with high cholesterol. Absence of
normal insulin-mediated but not sodium nitroprussideinduced
venodilation in hypercholesterolemia
suggests that insulin-mediated vasodilation is endothelium
dependent.
© 1998 American Heart Association, Inc.
Scientific Contributions
Insulin-Mediated Venodilation Is Impaired in Patients With High Cholesterol
Key Words: hypercholesterolemia vasoreactivity insulin norepinephrine endothelium
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