Metabolic vasodilation in the human forearm is preserved in hypercholesterolemia despite impairment of endothelium-dependent and independent vasodilation

Objective: Hypercholesterolemia has been shown to impair endothelium-mediat ed, nitric oxide (NO)-dependent responses to acetylcholine (ACh), serotonin , substance P and flow-mediated dilation. We have recently shown that NO co ntributes to metabolic vasodilation in the human forearm. We sought to dete rmine whether metabolic vasodilation is impaired in healthy subjects with h ypercholesterolemia. Methods: We compared the forearm blood flow (FBF) resp onses to isotonic exercise, ACh and the endothelium-independent vasodilator sodium nitroprusside in young, otherwise healthy volunteers with hyperchol esterolemia and controls before and after the NO inhibitor N-G-monomethyl-L -arginine (L-NMMA). FBF was measured using venous occlusion plethysmography , Hy percholesterolemic (n=20) and control(n=20) subjects were age- and gen der-matched. Results: Total cholesterol(6.9+/-0.3 vs. 4.6+/-0.1 mmol/l, P<0 .0001), low density lipoprotein (4.9+/-0.4 vs. 2.7+/-0.1 mmol/l, P<0.001) a nd triglyceride (1.3+/-0.2 vs. 0.8+/-0.1 mmol/l, P=0.005) levels were highe r in the hypercholesterolemic group. Basal FBF and resistance were similar in the two groups. Hypercholesterolemia impaired the peak FBF response to A Ch (11.1+/-1.9 vs. 17.6+/-2.2 ml/100 ml/min, P=0.03), and reduced the peak response to sodium nitroprusside (6.0=/-0.4 vs. 8.1+/-0.6 ml/100 ml/min, P< 0.01). However, hypercholesterolemia did not affect peak hyperemic FBF (13. 1+/-1.0 vs. 13.2+/-1.0 ml/100 ml/min, P=1.0) or the FBF volume repayment du ring the 1 or 5 min after exercise. Resting FBF was reduced by L-NMMA to a similar degree (by 33% vs. 40%, P=0.17) in both groups. Although L-NMMA red uced peak hyperemic FBF (by 16% vs. 17%, P=0.93) and the volume repaid afte r exercise in both groups, there were no differences between the two groups . Conclusions: Exercise-induced metabolic vasodilation is in part dependent on NO release. Hypercholesterolemia impairs NO-mediated vasodilation, but is not associated with a reduction in exercise-induced hyperemia. This may indicate that multiple compensatory mechanisms are operative in skeletal mu scle metabolic vasodilation. (C) 1999 Elsevier Science B.V. All rights rese rved.