Key Points
- To investigate whether insulin-mediated vasodilation in human skeletal muscle vasculature is driven by endothelium-derived nitric oxide.
- Infused the nitric oxide synthase inhibitor L-NMMA (16 mg/min) directly into the femoral artery of normal subjects during normal saline infusion or a euglycemic hyperinsulinemic clamp.
- Evaluated leg blood flow responses to graded intrafemoral infusions of methacholine chloride (endothelium-dependent) and sodium nitroprusside (endothelium-independent) during saline and hyperinsulinemic conditions.
- Intrafemoral L-NMMA reduced leg blood flow from 0.296 ± 0.032 to 0.235 ± 0.022 L/min during saline and from 0.479 ± 0.118 to 0.266 ± 0.052 L/min during hyperinsulinemia (P < 0.03), raising NO-dependent flow from ~20% to ~40% (P < 0.003).
- Leg blood flow increases to endothelium-dependent methacholine chloride were significantly augmented during hyperinsulinemia compared to saline (P < 0.03), whereas responses to sodium nitroprusside were not augmented.
Structured PICO
Is insulin-mediated skeletal muscle vasodilation dependent on endothelium-derived nitric oxide in normal subjects?
PPopulationNormal subjects
IInterventionN-monomethyl-L-arginine (L-NMMA) administered directly into the femoral artery at 16 mg/min during a euglycemic hyperinsulinemic clamp (HIC); graded intrafemoral artery infusions of methacholine chloride (MCh) or sodium nitroprusside (SNP)
CComparatorSaline infusion (NS)
OOutcomeLeg blood flow (LBF)surrogate
Insulin-mediated vasodilation in skeletal muscle is dependent on endothelium-derived nitric oxide, suggesting insulin acts as a novel modulator of the EDNO system.