title: Vascular function and endothelin-1: tipping the balance between vasodilation and vasoconstriction.
abstract: Endothelin-1 (ET-1), a potent vasoconstrictor secreted by vascular endothelial cells, has been implicated in the pathophysiology of numerous cardiovascular diseases, yet the direct impact of ET-1 on vascular function remains unclear. Therefore, in seven young (23 ± 1 yr) healthy subjects, we investigated the effect of an intra-arterial infusion of ET-1 on reactive hyperemia (RH) and flow-mediated dilation (FMD) in the popliteal artery following 5 min of suprasystolic cuff occlusion. ET-1 infusion significantly attenuated basal leg blood flow (control: 62 ± 4 ml/min, ET-1: 47 ± 9 ml/min), RH [area-under-curve (AUC); control: 162 ± 15 ml, ET-1: 104 ± 16 ml], and peak RH (control: 572 ± 51 ml/min, ET-1: 412 ± 32 ml/min) (P< 0.05). Administration of ET-1 also reduced FMD (control: 2.4 ± 0.3%, ET-1: 0.5 ± 0.5%) and FMD normalized for shear rate (control: 10.5 × 10-4± 2.0 × 10-4%/s-1, ET-1: 0.9 × 10-4± 2.8 ×10-4%/s-1). These findings reveal that elevated levels of ET-1 have a significant impact on vascular function, indicating that studies employing RH and FMD as markers of microvascular function and nitric oxide bioavailability, respectively, should exercise caution, as ET-1 can impact these assessments by tipping the balance between vasodilation and vasoconstriction, in favor of the latter.NEW & NOTEWORTHYEndothelin-1 (ET-1) is recognized as the body's most potent endogenous vasoconstrictor, but the impact of this peptide on vascular function is not well understood. The present study revealed that the intra-arterial administration of ET-1 impaired both microvascular and conduit vessel function of the leg in young, healthy, humans. Studies employing vascular testing in patient cohorts that experience a disease-related increase in ET-1 should thus exercise caution, as ET-1 clearly impairs vascular function.
authors.affiliation: College of Osteopathic Medicine, Touro University, Henderson, Nevada.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Nishiyama
authors.affiliation: Department of Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah.|Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah; and.|Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
authors.affiliation: Department of Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah; r.richardson@hsc.utah.edu.|Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah; and.|Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
mesh_terms: D000328:Adult; D019332:Endothelin-1 / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D015444:Exercise / Q000502:physiology; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000188:drug therapy / Q000378:metabolism; D007261:Infusions, Intra-Arterial / Q000379:methods; D007866:Leg / Q000098:blood supply; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D011150:Popliteal Artery / Q000187:drug effects / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide
keywords: cardiovascular disease; endothelium; flow-mediated dilation; vascular function