The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine
Abstract
Despite its very potent vasodilating action in vivo, acetylcholine (ACh) does not always produce relaxation of isolated preparations of blood vessels in vitro. For example, in the helical strip of the rabbit descending thoracic aorta, the only reported response to ACh has been graded contractions, occurring at concentrations above 0.1 muM and mediated by muscarinic receptors. Recently, we observed that in a ring preparation from the rabbit thoracic aorta, ACh produced marked relaxation at concentrations lower than those required to produce contraction (confirming an earlier report by Jelliffe). In investigating this apparent discrepancy, we discovered that the loss of relaxation of ACh in the case of the strip was the result of unintentional rubbing of its intimal surface against foreign surfaces during its preparation. If care was taken to avoid rubbing of the intimal surface during preparation, the tissue, whether ring, transverse strip or helical strip, always exhibited relaxation to ACh, and the possibility was considered that rubbing of the intimal surface had removed endothelial cells. We demonstrate here that relaxation of isolated preparations of rabbit thoracic aorta and other blood vessels by ACh requires the presence of endothelial cells, and that ACh, acting on muscarinic receptors of these cells, stimulates release of a substance(s) that causes relaxation of the vascular smooth muscle. We propose that this may be one of the principal mechanisms for ACh-induced vasodilation in vivo. Preliminary reports on some aspects of the work have been reported elsewhere.
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Production of NO in basal conditions is largely regulated by the activity of endothelial NOS (eNOS) in the vascular endothelium.
“The production of NO in basal conditions is largely regulated by the activity of endothelial NOS (eNOS) in the vascular endothelium”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [324]
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- Authors
- Furchgott, R. F., & Zawadzki, J. V.
- Affiliations
- SUNY Downstate Health Sciences University (US)
- Venue
- Nature
- Published
- 1980-11
- Volume
- 288
- Issue
- 5789
- Pages
- 373-376
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2169182236
- Cited by
- 12,064
- References
- 1
- Citations by year
- 2026: 86 · 2025: 108 · 2024: 116 · 2023: 141 · 2022: 151 · 2021: 178 · 2020: 208 · 2019: 213 · 2018: 209 · 2017: 212 · 2016: 202 · 2015: 240 · 2014: 332 · 2013: 268 · 2012: 289
- FWCI
- 35.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- acetylcholine, endothelial cells, vasorelaxation, thoracic aorta, muscarinic receptors, endothelium-dependent vasodilation
- MeSH terms
- Acetylcholine, Animals, Hypoxia, Aorta, Thoracic, Microbial Collagenase, Endothelium, Male, Rabbits, Receptors, Cholinergic, Receptors, Muscarinic, Vasomotor System
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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