Vascular function in the forearm of hypercholesterolaemic patients off and on lipid-lowering medication

Lancet. 1995 Aug 19;346(8973):467-71. doi: 10.1016/s0140-6736(95)91322-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arginine / administration & dosage
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Blood Pressure
  • Cholesterol / blood
  • Cholestyramine Resin / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Forearm / blood supply*
  • Humans
  • Hyperlipoproteinemia Type II / drug therapy*
  • Hyperlipoproteinemia Type II / physiopathology*
  • Hypolipidemic Agents / therapeutic use*
  • Infusions, Intravenous
  • Lovastatin / analogs & derivatives*
  • Lovastatin / therapeutic use
  • Male
  • Nitroprusside / administration & dosage
  • Nitroprusside / pharmacology
  • Regional Blood Flow / physiology
  • Serotonin / administration & dosage
  • Serotonin / pharmacology
  • Simvastatin
  • Vasodilation / drug effects
  • Vasodilation / physiology
  • omega-N-Methylarginine


  • Hypolipidemic Agents
  • Cholestyramine Resin
  • Nitroprusside
  • omega-N-Methylarginine
  • Serotonin
  • Arginine
  • Cholesterol
  • Lovastatin
  • Simvastatin