title: Contribution of endothelium-derived hyperpolarizing factor to exercise-induced vasodilation in health and hypercholesterolemia.
abstract: 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:
authors: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors: Muhiddin A
authors: MA
authors: Ozkor
authors: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors: Salim S
authors: SS
authors: Hayek
authors: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors: Ayaz M
authors: AM
authors: Rahman
authors: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors: Jonathan R
authors: JR
authors: Murrow
authors: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors: Nino
authors: N
authors: Kavtaradze
authors: Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors: Ji
authors: J
authors: Lin
authors: Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors: Amita
authors: A
authors: Manatunga
authors: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA aquyyum@emory.edu.
authors: Arshed A
authors: AA
authors: Quyyumi
mesh_terms: D000328:Adult; D001685:Biological Factors / Q000378:metabolism*; D001783:Blood Flow Velocity; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D015444:Exercise; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000008:administration & dosage; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism; D012039:Regional Blood Flow; D015398:Signal Transduction; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D001685:Biological Factors; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D019001:Nitric Oxide Synthase
keywords: endothelial function; endothelium-derived hyperpolarizing factor; exercise; hypercholesterolemia; nitric oxide; vasodilation
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