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 - Funding Information:
National Institutes of Health Research Grant RO1 HL79115, PHS Grant UL1 RR025008 from the Clinical and Translational Science Award Program, and PHS Grant M01 RR00039 from the General Clinical Research Center Program, National Institutes of Health, National Center for Research Resources, British Cardiovascular Society Research Fellowship, and the National Blood Foundation.
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 -