Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase

Circulation. 2001 Jul 17;104(3):342-5. doi: 10.1161/01.cir.104.3.342.

Abstract

Background: Insulin resistance and arterial hypertension are related, but the underlying mechanism is unknown. Endothelial nitric oxide synthase (eNOS) is expressed in skeletal muscle, where it may govern metabolic processes, and in the vascular endothelium, where it regulates arterial pressure.

Methods and results: To study the role of eNOS in the control of the metabolic action of insulin, we assessed insulin sensitivity in conscious mice with disruption of the gene encoding for eNOS. eNOS(-/-) mice were hypertensive and had fasting hyperinsulinemia, hyperlipidemia, and a 40% lower insulin-stimulated glucose uptake than control mice. Insulin resistance in eNOS(-/-) mice was related specifically to impaired NO synthesis, because in equally hypertensive 1-kidney/1-clip mice (a model of renovascular hypertension), insulin-stimulated glucose uptake was normal.

Conclusions: These results indicate that eNOS is important for the control not only of arterial pressure but also of glucose and lipid homeostasis. A single gene defect, eNOS deficiency, may represent the link between metabolic and cardiovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries
  • Blood Flow Velocity / drug effects
  • Blood Flow Velocity / physiology
  • Blood Glucose / drug effects
  • Body Weight
  • Disease Models, Animal
  • Glucose / metabolism
  • Glucose / pharmacokinetics
  • Glucose Clamp Technique
  • Hindlimb / blood supply
  • Homozygote
  • Hyperinsulinism / complications
  • Hyperinsulinism / genetics
  • Hyperlipidemias / complications
  • Hyperlipidemias / genetics*
  • Hypertension / complications
  • Hypertension / genetics*
  • Hypertension, Renovascular / metabolism
  • In Vitro Techniques
  • Insulin / pharmacology
  • Insulin Resistance / genetics*
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / metabolism
  • Nitrates / blood
  • Nitric Oxide Synthase / deficiency*
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nitrites / blood

Substances

  • Blood Glucose
  • Insulin
  • Nitrates
  • Nitrites
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Glucose