TY - JOUR
T1 - Contribution of endothelium-derived hyperpolarizing factor to exercise-induced vasodilation in health and hypercholesterolemia
AU - Ozkor, Muhiddin A.
AU - Hayek, Salim S.
AU - Rahman, Ayaz M.
AU - Murrow, Jonathan R.
AU - Kavtaradze, Nino
AU - Lin, Ji
AU - Manatunga, Amita
AU - Quyyumi, Arshed A.
N1 - Publisher Copyright:
© The Author(s) 2015.
PY - 2015/2/15
Y1 - 2015/2/15
N2 - 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.
AB - 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.
KW - endothelial function
KW - endothelium-derived hyperpolarizing factor
KW - exercise
KW - hypercholesterolemia
KW - nitric oxide
KW - vasodilation
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U2 - 10.1177/1358863X14565374
DO - 10.1177/1358863X14565374
M3 - Article
C2 - 25648989
AN - SCOPUS:84924854674
SN - 1358-863X
VL - 20
SP - 14
EP - 22
JO - Vascular Medicine (United Kingdom)
JF - Vascular Medicine (United Kingdom)
IS - 1
ER -