title: Both flow-mediated dilation and constriction are associated with changes in blood flow and shear stress: Two complementary perspectives on endothelial function.
abstract: BACKGROUND
  Flow-mediated dilation (FMD) quantifies endothelium-dependent vasomotor responses to short-term increases in blood flow. Low-flow mediated vasoconstriction (L-FMC) has been more recently introduced as additional measure of endothelial function, and its relationship with changes in blood flow, cardiovascular risk factors and FMD ha∧s been less well characterized.
  
  
  METHODS
  We evaluated radial artery FMD and L-FMC along with the changes in blood flow and shear rate/stress in 584 patients with known or suspected coronary artery disease (72.9% men, mean age 67+/-11 years). Baseline blood flow and shear rate showed a modest association with radial artery FMD and L-FMC (R2 = 0.04 and R2 = 0.02, P < 0.0001). Resting diameter showed a stronger association with FMD but not with L-FMC (R2 = 0.11, P < 0.0001 and R2 = 0.005, P = 0.09). Analysis with generalized additive models showed that age, sex and presence and extent of coronary artery disease were strongly related to both endothelial function measures (P < 0.001 for both), but they explained only 12.4% and 10.1% of the variance in L-FMC and FMD. When the corresponding changes in blood flow were added to these statistical models, the % of variance explained raised to 20.4% and 17.7% for L-FMC and FMD. L-FMC was a strong predictor of FMD even after correction for the changes in blood flow.
  
  
  CONCLUSIONS
  Changes in blood flow are the most important determinants of both L-FMC and FMD. These observations support the concept that both FMD and L-FMC measure endothelium-dependent, shear-induced, vasomotion.
authors.affiliation: Kardiologie I, Zentrum für Kardiologie und DZHK Standort Rhein-Main, Mainz, Germany.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Gori
authors.affiliation: Kardiologie I, Zentrum für Kardiologie und DZHK Standort Rhein-Main, Mainz, Germany.
authors.forename: Urs
authors.initials: U
authors.lastname: von Henning
authors.affiliation: Kardiologie I, Zentrum für Kardiologie und DZHK Standort Rhein-Main, Mainz, Germany.
authors.forename: Selina
authors.initials: S
authors.lastname: Muxel
authors.affiliation: Kardiologie I, Zentrum für Kardiologie und DZHK Standort Rhein-Main, Mainz, Germany.
authors.forename: Sarina
authors.initials: S
authors.lastname: Schaefer
authors.affiliation: Kardiologie I, Zentrum für Kardiologie und DZHK Standort Rhein-Main, Mainz, Germany.
authors.forename: Federica
authors.initials: F
authors.lastname: Fasola
authors.affiliation: Kardiologie I, Zentrum für Kardiologie und DZHK Standort Rhein-Main, Mainz, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Vosseler
authors.affiliation: Kardiologie I, Zentrum für Kardiologie und DZHK Standort Rhein-Main, Mainz, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Schnorbus
authors.affiliation: Institut für Medizinische Biometrie, Epidemiologie und Informatik, University Medical Center Mainz, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Binder
authors.affiliation: Department of Medicine, Division of Cardiology, Mount Sinai and University Health Network Hospitals, University of Toronto, Canada.
authors.forename: John D
authors.initials: JD
authors.lastname: Parker
authors.affiliation: Kardiologie I, Zentrum für Kardiologie und DZHK Standort Rhein-Main, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
mesh_terms: D000368:Aged; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow; D012307:Risk Factors; D013314:Stress, Mechanical; D014661:Vasoconstriction / Q000276:immunology*
keywords: Endothelium/vascular type/nitric oxide; coronary circulation; pathophysiology