Selective Impairment of Nitric Oxide Dependent Vasodilation in Young Adults with Hypercholesterolemia

Abstract

Objective To investigate comparatively flow response of resistance arteries to exogenous and endogenous nitric oxide in young adults with high serum cholesterol.

Background Impaired vascular effectiveness of endogenous and exogenous nitric oxide may be considered to unmask impairment of its anti-atherogenic properties. It may thus represent a valuable early diagnostic index for these young adults at high risk for developing atherosclerosis.

Methods In 10 patients with elevated plasma levels of low-density lipoprotein (high cholesterol group, age 34 ± 5 year; (mean ± SEM) level of low-density lipoprotein 5.2 ± 0.5 mmol/l) and 12 age-matched control individuals (control group, 34 ± 3 years; level of low-density lipoprotein <3.9 mmol/l), forearm blood flow was measured by venous occlusion plethysmography at rest, during reactive hyperaemia after 3 min no-flow ischaemia, and during local intra-arterial infusions of acetylcholine, bradykinin, sodium nitroprusside and adenosine in increasing doses.

Results In both' groups resting forearm blood flow was similar and was dose-dependently increased by each vasodilator. In the hypercholesterolaemic patients compared with control subjects maximal forearm blood flow was significantly impaired after stimulation of endogenous nitric oxide synthesis by acetylcholine and bradykinin and during infusion of the nitric oxide donor sodium nitroprusside (acetylcholine: −19%, bradykinin: −29%, sodium nitroprusside; 5924% versus control individuals: P < 0.05). In contrast, adenosine-dependent vasodilation and peak flow during reactive hyperaemia were similar in both groups.

Conclusion Excess of low-density lipoprotein cholesterol leads to selective impairment of nitric oxide-dependent vasodilation even in young adults, whereas adenylylcyclase-dependent vasodilation of vascular smooth muscle and maximal dilatory capacity are preserved. In view of the anti-atherogenic properties of nitric oxide, it appears highly desirable to detect this selective vascular dysfunction early in these young adults at high risk of developing atherosclerotic lesions.