L-arginine normalizes endothelial function in cerebral vessels from hypercholesterolemic rabbits.
Open accessAbstract
We hypothesized that normal vascular reactivity could be restored in vessels from hypercholesterolemic animals by exposing them to L-arginine, the precursor of endothelium-derived relaxing factor (EDRF). Basilar arteries were harvested from New Zealand white rabbits fed normal chow or that supplemented with 2% cholesterol for 10 wk. Vessels were cannulated for perfusion at physiologic pressure. Changes in vessel diameter were monitored by videomicroscopy. In comparison to normal vessels, those from hypercholesterolemic animals vasoconstricted more to KCl, endothelin (E), and 5-hydroxytryptamine (5-HT). Conversely, vasodilation to acetylcholine (ACh) (but not that to verapamil) was significantly impaired in the hypercholesterolemic animals. In vitro administration of L-arginine (3 mM) for 45 min normalized vasodilation to ACh and vasoconstriction to E, 5-HT, and KCl in the isolated vessels from hypercholesterolemic animals. This effect was stereospecific, since D-arginine had no effect. To conclude, these data confirm that hypercholesterolemia attenuates endothelium-derived relaxation, and enhances the sensitivity of these vessels to vasoconstrictors. In vitro administration of L-arginine normalized vascular reactivity of isolated vessels from hypercholesterolemic animals. Thus, hypercholesterolemia induces a reversible endothelial dysfunction that may be corrected by supplying the precursor of EDRF, L-arginine.
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- Authors
- Rossitch, E., Alexander, E., Black, P. M., & Cooke, J. P.
- Affiliations
- Brigham and Women's Hospital (US)
- Stanford University (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 1991-04-01
- Volume
- 87
- Issue
- 4
- Pages
- 1295-1299
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2001785527
- Cited by
- 161
- References
- 26
- Citations by year
- 2025: 1 · 2023: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 10.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (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
- L-arginine, endothelial dysfunction, hypercholesterolemia, endothelium-derived relaxing factor, nitric oxide, cerebral vasculature, basilar artery, acetylcholine-induced vasodilation, endothelin, vasoconstriction, cholesterol-fed rabbits, D-arginine
- MeSH terms
- Acetylcholine, Animals, Arginine, Endothelium, Vascular, Hypercholesterolemia, Nitric Oxide, Potassium Chloride, Rabbits, Serotonin, Vasodilation, Verapamil
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