ArticleJournal of applied physiology (Bethesda, Md. : 1985)2015
Endothelial-derived hyperpolarization contributes to acetylcholine-mediated vasodilation in human skin in a dose-dependent manner.
Article in Journal of applied physiology (Bethesda, Md. : 1985), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 36 citations in OpenAlex.
- Severe Hypouricemia Impairs Endothelium-Dependent Vasodilatation and Reduces Blood Pressure in Healthy Young Men: A Randomized, Placebo-Controlled, and Crossover Study.Journal of the American Heart Association · 2019Trial
- Effects of supervised exercise training on lower-limb cutaneous microvascular reactivity in adults with venous ulcers.European journal of applied physiology · 2018Trial
- Methods for analyzing acetylcholine-induced vasodilation in human skin.Journal of applied physiology (Bethesda, Md. : 1985) · 2026Article
- Heat Therapy: Targeting Health, Disease, and Disability.Comprehensive Physiology · 2026Review
- Beneficial Effects of Cocoa Flavanols on Microvascular Responses in Young Men May Be Dependent on Ethnicity and Lifestyle.Nutrients · 2024Article
- The peripheral vascular responses in non-freezing cold injury and matched controls.Experimental physiology · 2023Article
- Delayed Cutaneous Microvascular Responses With Non-consecutive 3 Days of Remote Ischemic Preconditioning.Frontiers in physiology · 2022Article
- Inhibition of iNOS augments cutaneous endothelial NO-dependent vasodilation in prehypertensive non-Hispanic Whites and in non-Hispanic Blacks.American journal of physiology. Heart and circulatory physiology · 2021Article
- Healthy active older adults have enhanced KAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Blood pressure normalization via pharmacotherapy improves cutaneous microvascular function through NO-dependent and NO-independent mechanisms.Microcirculation (New York, N.Y. : 1994) · 2017Article
- Ten days of repeated local forearm heating does not affect cutaneous vascular function.Journal of applied physiology (Bethesda, Md. : 1985) · 2017Article
- The roles of KAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2017Article
- K+ channel mechanisms underlying cholinergic cutaneous vasodilation and sweating in young humans: roles of KCa, KATP, and KV channels?American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- Cutaneous vascular and sweating responses to intradermal administration of prostaglandin E1 and E2 in young and older adults: a role for nitric oxide?American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
Cutaneous acetylcholine (ACh)-mediated dilation is commonly used to assess microvascular function, but the mechanisms of dilation are poorly understood. Depending on dose and method of administration, nitric oxide (NO) and prostanoids are involved to varying extents and the roles of endothelial-derived hyperpolarizing factors (EDHFs) are unclear. In the present study, five incremental doses of ACh (0.01-100 mM) were delivered either as a 1-min bolus (protocol 1, n = 12) or as a ≥20-min continuous infusion (protocol 2, n = 10) via microdialysis fibers infused with 1) lactated Ringer, 2) tetraethylammonium (TEA) [a calcium-activated potassium channel (KCa) and EDHF inhibitor], 3) L-NNA+ketorolac [NO synthase (NOS) and cyclooxygenase (COX) inhibitors], and 4) TEA+L-NNA+Ketorolac. The hyperemic response was characterized as peak and area under the curve (AUC) cutaneous vascular conductance (CVC) for bolus infusions or plateau CVC for continuous infusions, and reported as %maximal CVC. In protocol 1, TEA, alone and combined with NOS+COX inhibition, attenuated peak CVC (100 mM Ringer 59 ± 6% vs. TEA 43 ± 5%, P < 0.05; L-NNA+ketorolac 35 ± 4% vs. TEA+L-NNA+ketorolac 25 ± 4%, P < 0.05) and AUC (Ringer 25,414 ± 3,528 vs. TEA 21,403 ± 3,416%·s, P < 0.05; L-NNA+ketorolac 25,628 ± 3,828%(.)s vs. TEA+L-NNA+ketorolac 20,772 ± 3,711%·s, P < 0.05), although these effects were only significant at the highest dose of ACh. At lower doses, TEA lengthened the total time of the hyperemic response (10 mM Ringer 609 ± 78 s vs. TEA 860 ± 67 s, P < 0.05). In protocol 2, TEA alone did not affect plateau CVC, but attenuated plateau in combination with NOS+COX inhibition (100 mM 50.4 ± 6.6% vs. 30.9 ± 6.3%, P < 0.05). Therefore, EDHFs contribute to cutaneous ACh-mediated dilation, but their relative contribution is altered by the dose and infusion procedure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.