Esg. Stroes et al., VASCULAR FUNCTION IN THE FOREARM OF HYPERCHOLESTEROLEMIC PATIENTS OFFAND ON LIPID-LOWERING MEDICATION, Lancet, 346(8973), 1995, pp. 467-471
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.