VASCULAR FUNCTION IN THE FOREARM OF HYPERCHOLESTEROLEMIC PATIENTS OFFAND ON LIPID-LOWERING MEDICATION

To study whether vascular dysfunction in hypercholesterolaemia is reve rsible, we investigated patients without overt arterial disease who we re taking maintenance treatment for hypercholesterolaemia. Medication was stopped for 2 weeks, reinstituted for 12 weeks, and again stopped for 6 weeks. During both maintenance treatment and the 12 weeks of ste p-up medication the lipid profile was improved but did not return to n ormal. Dose-response curves for serotonin-induced vasodilatation, an i ndex of nitric oxide-dependent vasodilatation, showed a comparable and significant rightward shift. after a medication-free period of 2 and 6 weeks compared with control subjects, indicating endothelial dysfunc tion, which was already maximum after 2 weeks. After 12 weeks of lipid -lowering medication, the difference in endothelial function between c ontrols and patients had disappeared. Go-infusion of L-arginine, the s ubstrate for nitric oxide synthase, returned the impaired serotonin re sponse during hypercholesterolaemia to normal, but had no effect on th is response in controls or in patients while on lipid-lowering medicat ion. Neither endothelium-independent vasorelaxation, assessed by sodiu m nitroprusside infusion, nor vasoconstriction induced by the nitric o xide blocker L-NMMA, were different between controls and patients, whe ther the latter were on or off lipid-lowering medication. Our results show an L-arginine-sensitive, impaired nitric-oxide-mediated vascular relaxation of forearm resistance vessels in hypercholesterolaemia whic h is reproducible, and reversible after short-term lipid-lowering ther apy. Demonstration of such changes in this readily accessible vascular bed will allow larger trials assessing vascular function during lipid -lowering therapy to be done.