Contribution of endothelium-derived hyperpolarizing factor to exercise-induced vasodilation in health and hypercholesterolemia

Muhiddin A. Ozkor, Salim S. Hayek, Ayaz M. Rahman, Jonathan R. Murrow, Nino Kavtaradze, Ji Lin, Amita Manatunga, Arshed A. Quyyumi

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The role of endothelium-derived hyperpolarizing factor (EDHF) in either the healthy circulation or in those with hypercholesterolemia is unknown. In healthy and hypercholesterolemic subjects, we measured forearm blood flow (FBF) using strain-gauge plethysmography at rest, during graded handgrip exercise, and after sodium nitroprusside infusion. Measurements were repeated after l-NMMA, tetraethylammonium (TEA), and combined infusions. At rest, l-NMMA infusion reduced FBF in healthy but not hypercholesterolemic subjects. At peak exercise, vasodilation was lower in hypercholesterolemic compared to healthy subjects (274% vs 438% increase in FBF, p=0.017). TEA infusion reduced exercise-induced vasodilation in both healthy and hypercholesterolemic subjects (27%, p<0.0001 and -20%, p<0.0001, respectively). The addition of l-NMMA to TEA further reduced FBF in healthy (-14%, p=0.012) but not in hypercholesterolemic subjects, indicating a reduced nitric oxide and greater EDHF-mediated contribution to exercise-induced vasodilation in hypercholesterolemia. In conclusion, exercise-induced vasodilation is impaired and predominantly mediated by EDHF in hypercholesterolemic subjects. Clinical Trial Registration Identifier: NCT00166166.

Original languageEnglish (US)
Pages (from-to)14-22
Number of pages9
JournalVascular Medicine
Issue number1
StatePublished - Feb 15 2015
Externally publishedYes


  • endothelial function
  • endothelium-derived hyperpolarizing factor
  • exercise
  • hypercholesterolemia
  • nitric oxide
  • vasodilation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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