Hypertension in mice lacking the gene for endothelial nitric oxide synthase
Abstract
Nitric oxide (NO), a potent vasodilator produced by endothelial cells, is thought to be the endothelium-dependent relaxing factor (EDRF) which mediates vascular relaxation in response to acetylcholine, bradykinin and substance P in many vascular beds. NO has been implicated in the regulation of blood pressure and regional blood flow, and also affects vascular smooth-muscle proliferation and inhibits platelet aggregation and leukocyte adhesion. Abnormalities in endothelial production of NO occur in atherosclerosis, diabetes and hypertension. Pharmacological blockade of NO production with arginine analogues such as L-nitroarginine (L-NA) or L-N-arginine methyl ester affects multiple isoforms of nitric oxide synthase (NOS), and so cannot distinguish their physiological roles. To study the role of endothelial NOS (eNOS) in vascular function, we disrupted the gene encoding eNOS in mice. Endothelium-derived relaxing factor activity, as assayed by acetylcholine-induced relaxation, is absent, and the eNOS mutant mice are hypertensive. Thus eNOS mediates basal vasodilation. Responses to NOS blockade in the mutant mice suggest that non-endothelial isoforms of NOS may be involved in maintaining blood pressure.
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eNOS is the constitutive NOS form in endothelial cells and the main contributor to vascular NO levels in physiological conditions.
“eNOS is the constitutive NOS form in endothelial cells (ECs), and as such, it is the main contributor to vascular NO levels in physiological conditions”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [446]
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- Authors
- Huang, P. L., Huang, Z., Mashimo, H., Bloch, K. D., Moskowitz, M. A., Bevan, J. A., & Fishman, M. C.
- Affiliations
- Massachusetts General Hospital (US)
- Harvard University (US)
- University of Vermont (US)
- Venue
- Nature
- Published
- 1995-09
- Volume
- 377
- Issue
- 6546
- Pages
- 239-242
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2091193879
- Cited by
- 2,070
- References
- 27
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 27 · 2023: 32 · 2022: 29 · 2021: 50 · 2020: 52 · 2019: 52 · 2018: 34 · 2017: 44 · 2016: 47 · 2015: 58 · 2014: 60 · 2013: 63 · 2012: 82
- FWCI
- 43.74
- 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 › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- endothelial nitric oxide synthase, eNOS knockout mice, hypertension, nitric oxide, endothelium-derived relaxing factor, acetylcholine-induced relaxation, vasodilation, blood pressure regulation, nitric oxide synthase isoforms, L-arginine analogues, vascular function
- MeSH terms
- Amino Acid Oxidoreductases, Animals, Aorta, Arginine, Blood Pressure, Endothelium, Vascular, Homeostasis, Hypertension, Mutation, Vasodilation, Nitric Oxide Synthase, Mice, In Vitro Techniques
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