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: Muhiddin A Ozkor, Salim S Hayek, Ayaz M Rahman, Jonathan R Murrow, Nino Kavtaradze, Ji Lin, Amita Manatunga, Arshed A Quyyumi
• Journal: Vascular medicine (London, England) (Vasc Med) Vol. 20 Issue 1 Pg. 14-22 (Feb 2015) ISSN: 1477-0377 [Electronic] England
• PMID: 25648989 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2015.

Chemical References

• Biological Factors
• Enzyme Inhibitors
• Potassium Channel Blockers
• Potassium Channels, Calcium-Activated
• Vasodilator Agents
• endothelium-dependent hyperpolarization factor
• Nitric Oxide Synthase

Topics

• Adult
• Biological Factors (metabolism)
• Blood Flow Velocity
• Endothelium, Vascular (drug effects, metabolism, physiopathology)
• Enzyme Inhibitors (administration & dosage)
• Exercise
• Female
• Forearm (blood supply)
• Humans
• Hypercholesterolemia (blood, diagnosis, physiopathology)
• Infusions, Intra-Arterial
• Male
• Middle Aged
• Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
• Potassium Channel Blockers (administration & dosage)
• Potassium Channels, Calcium-Activated (antagonists & inhibitors, metabolism)
• Regional Blood Flow
• Signal Transduction
• Time Factors
• Vasodilation (drug effects)
• Vasodilator Agents (administration & dosage)
• Young Adult