Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Abstract
Endothelium-derived relaxing factor (EDRF) is a labile humoral agent which mediates the action of some vasodilators. Nitrovasodilators, which may act by releasing nitric oxide (NO), mimic the effect of EDRF and it has recently been suggested by Furchgott that EDRF may be NO. We have examined this suggestion by studying the release of EDRF and NO from endothelial cells in culture. No was determined as the chemiluminescent product of its reaction with ozone. The biological activity of EDRF and of NO was measured by bioassay. The relaxation of the bioassay tissues induced by EDRF was indistinguishable from that induced by NO. Both substances were equally unstable. Bradykinin caused concentration-dependent release of NO from the cells in amounts sufficient to account for the biological activity of EDRF. The relaxations induced by EDRF and NO were inhibited by haemoglobin and enhanced by superoxide dismutase to a similar degree. Thus NO released from endothelial cells is indistinguishable from EDRF in terms of biological activity, stability, and susceptibility to an inhibitor and to a potentiator. We suggest that EDRF and NO are identical.
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NOX2 expression has been reported in other cell types including endothelial cells and adventitial fibroblasts.
“NOX2 expression has been also reported in other cell types including endothelial cells and adventitial fibroblasts (376, 382, 657, 714, 715, 736, 876) (FIGURE 9, Table 5).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [715]
Nitric oxide has a vasodilatory role.
“This paper described the vasodilatory role of nitric oxide.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [179]
NO synthesized by NOS in the endothelium diffuses into the vessel wall, activates soluble guanylate cyclase in vascular smooth muscle, raises cyclic GMP, and elicits relaxation of the vessel.
“NO synthesized by NOS in the endothelium diffuses into the vessel wall where it activates sGC in vascular smooth muscle; this leads to a rise in cyclic GMP (cGMP) and elicits relaxation of the vessel [96-102].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [102]
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Self-citationHambrecht, R., Fiehn, E., Weigl, C., Gielen, S., Hamann, C., Kaiser, R., Yu, J., Adams, V., Niebauer, J., & Schuler, G. C. (1998) · Circulation · doi:10.1161/01.cir.98.24.2709 · Cited by 963 · see citing works
Leeb-Lundberg, L. M. F., Marceau, F., Müller‐Esterl, W., Pettibone, D. J., & Zuraw, B. L. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.1.2 · Cited by 942 · see citing works
de Tejada, I. S., Goldstein, I., Azadzoi, K. M., Krane, R. J., & Cohen, R. A. (1989) · New England Journal of Medicine · doi:10.1056/nejm198904203201601 · Cited by 944 · see citing works
- Authors
- Palmer, R. M. J., Ferrige, A. G., & Moncada, S.
- Affiliations
- Wellcome Trust (GB)
- Venue
- Nature
- Published
- 1987-06
- Volume
- 327
- Issue
- 6122
- Pages
- 524-526
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2007737411
- Cited by
- 10,704
- References
- 0
- Citations by year
- 2026: 60 · 2025: 81 · 2024: 91 · 2023: 124 · 2022: 138 · 2021: 131 · 2020: 134 · 2019: 143 · 2018: 146 · 2017: 165 · 2016: 160 · 2015: 193 · 2014: 211 · 2013: 227 · 2012: 260
- FWCI
- 210.31
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- endothelium-derived relaxing factor, nitric oxide, endothelial cells, vasodilation, nitrovasodilators, bradykinin, superoxide dismutase, hemoglobin, chemiluminescence, ozone reactions
- MeSH terms
- Animals, Aorta, Bradykinin, Endothelium, Hemoglobins, Humans, Kinetics, Muscle Relaxation, Muscle, Smooth, Vascular, Nitric Oxide, Rabbits, Swine, Vasodilator Agents, In Vitro Techniques
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