INSULIN-MEDIATED VENODILATION IS IMPAIRED IN PATIENTS WITH HIGH CHOLESTEROL

Citation
Bh. Sung et al., INSULIN-MEDIATED VENODILATION IS IMPAIRED IN PATIENTS WITH HIGH CHOLESTEROL, Hypertension, 31(6), 1998, pp. 1266-1271
Citations number
29
Categorie Soggetti
Peripheal Vascular Diseas
Journal title
ISSN journal
0194911X
Volume
31
Issue
6
Year of publication
1998
Pages
1266 - 1271
Database
ISI
SICI code
0194-911X(1998)31:6<1266:IVIIIP>2.0.ZU;2-O
Abstract
Recently we have reported that insulin attenuates norepinephrine (NE)- induced vasoconstriction via a cyclic GMP-NO synthase pathway. Because hypercholesterolemia has been associated with abnormal endothelial fu nction, we investigated whether insulin-mediated vasodilation is impai red in hypercholesterolemia. To assess vasoreactivity, NE (12.5, 25, 5 0, and 100 ng/min), NE (100 ng/min) combined with insulin (8, 16, 24, and 32 mu U/min), and NE (100 ng/min) combined with sodium nitroprussi de (0.01, 0.1, 1, 10, and 100 ng/min) were infused into dorsal hand ve ins. Changes in venous diameter were measured by ultrasonography, usin g a 7.5-MHz transducer. Twenty-two healthy, normotensive hypercholeste rolemic subjects (HC; mean total cholesterol 6.93 mmol/L, HDL 1.45 mmo l/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. Baseli ne vein diameters were similar between groups, and the vasoconstrictor response to NE was not significantly different between HC and NC. Ins ulin significantly attenuated NE-induced vasoconstriction in NC but no t in HC (P<0.01). Both groups were able to venodilate with sodium nitr oprusside. To investigate the effects of cholesterol reduction on vasc ular reactivity, venoreactivity studies were repeated in 12 HC after t reatment with 20 to 40 mg/d lovastatin for 6 weeks. There were no sign ificant venoreactivity changes with the treatment. Plasma LDL choleste rol concentration was inversely correlated to venodilator effect of in sulin (r=-0.42, P<0.02). In conclusion, insulin-mediated vasodilation is impaired in patients with high cholesterol. Absence of normal insul in-mediated but not sodium nitroprusside-induced venodilation in hyper cholesterolemia suggests that insulin-mediated vasodilation is endothe lium dependent.