Vascular function in the forearm of hypercholesterolaemic patients off and on lipid-lowering medication.
To study whether vascular dysfunction in hypercholesterolaemia is reversible, we investigated patients without overt arterial disease who were 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 step-up medication the lipid profile was improved but did not return to normal. Dose-response curves for serotonin-induced vasodilatation, an index 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 dysfunction, which was already maximum after 2 weeks. After 12 weeks of lipid-lowering medication, the difference in endothelial function between controls and patients had disappeared. Co-infusion of L-arginine, the substrate for nitric oxide synthase, returned the impaired serotonin response during hypercholesterolaemia to normal, but had no effect on this response in controls or in patients while on lipid-lowering medication. Neither endothelium-independent vasorelaxation, assessed by sodium nitroprusside infusion, nor vasoconstriction induced by the nitric oxide blocker L-NMMA, were different between controls and patients, whether 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 which is reproducible, and reversible after short-term lipid-lowering therapy. Demonstration of such changes in this readily accessible vascular bed will allow larger trials assessing vascular function during lipid-lowering therapy to be done.
Stroes
E S
ES
Department of Nephrology, University Hospital Utrecht, The Netherlands.
Koomans
H A
HA
de Bruin
T W
TW
Rabelink
T J
TJ
D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D002792:Cholestyramine Resin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000503:physiopathology*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D012039:Regional Blood Flow / Q000502:physiology; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology; D019821:Simvastatin; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine
D000960:Hypolipidemic Agents; D002792:Cholestyramine Resin; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D012701:Serotonin; D001120:Arginine; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin