Impaired endothelium-dependent vasodilation in type 2 diabetes mellitus and the lack of effect of simvastatin

Cardiovasc Res. 2001 Nov;52(2):299-305. doi: 10.1016/s0008-6363(01)00379-0.

Abstract

Objective: Although type 2 diabetes is recognized as an independent risk factor for cardiovascular disease and cardiovascular disease is associated with endothelial dysfunction, the influence of type 2 diabetes per se on the endothelial function is controversial. HMG-CoA-reductase inhibitors have been shown to have short-term beneficial effects on endothelial dysfunction among patients with dyslipidemia or cardiovascular disease. The effect of HMG-CoA reductase inhibitors on the endothelial function in diabetes is largely unknown.

Methods: Seventeen patients with type 2 diabetes, free of cardiovascular disease and no other cardiovascular risk factors, except for dyslipidemia, were studied together with ten healthy volunteers. The effect of 5-hydroxytryptamine, as an endothelium-dependent vasodilator, and sodium nitroprusside, as an endothelium-independent vasodilator, on the forearm blood flow was measured using venous occlusion plethysmography.

Results: 5-Hydroxytryptamine and sodium nitroprusside, infused in the brachial artery, caused a dose-dependent vasodilation. The vasodilator response to 5-hydroxytryptamine was significantly lower among the diabetic patients, 42 and 56%, than among the controls, 73 and 103%, at a dose of 0.3 and 0.9 ng/kg/min, respectively (P<0.05 and P<0.001). Vasodilator responses to sodium nitroprusside were comparable among the diabetic patients and controls. A 6-week treatment with simvastatin 40 mg once daily did not change the vasodilator responses to 5-hydroxytryptamine or sodium nitroprusside among the patients with diabetes.

Conclusions: The results of this study indicate that the endothelial function is impaired in type 2 diabetes and is not restored after a 6-week treatment period with simvastatin 40 mg.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / physiopathology*
  • Forearm / blood supply
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Nitric Oxide Donors
  • Nitroprusside
  • Plethysmography
  • Regional Blood Flow / drug effects
  • Serotonin
  • Simvastatin / therapeutic use*
  • Treatment Failure
  • Triglycerides / blood
  • Vasodilator Agents

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Nitric Oxide Donors
  • Triglycerides
  • Vasodilator Agents
  • Nitroprusside
  • Serotonin
  • Simvastatin