L-arginine availability determines the duration of acetylcholine-induced systemic vasodilatation in vivo
Open accessAbstract
In vitro studies have shown that acetylcholine-induced vasorelaxation is mediated by endothelium-derived relaxing factor/nitric oxide (EDRF/NO). EDRF/NO is synthesized from L-arginine by an enzymatic pathway that is inhibited by L-NG-methylarginine. To assess whether EDRF/NO also mediates the vasodilating action of acetylcholine in vivo, we have investigated the effect of L-arginine and L-NG-methylarginine on the hypotensive response to acetylcholine in the anesthetized guinea pig. L-arginine prolonged the duration of the depressor response to acetylcholine and L-NG-methylarginine decreased it. However, neither L-arginine nor L-NG-methylarginine modified the magnitude of acetylcholine's hypotensive effect unless the blood pressure was previously elevated by infusion with norepinephrine. Thus, de novo synthesis of nitric oxide from L-arginine contributes importantly, but not exclusively, to acetylcholine's hypotensive effect in the guinea pig. Furthermore, the concentration of circulating L-arginine may influence the duration and magnitude of acetylcholine-induced depressor responses under normotensive and hypertensive conditions.
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Most cells have intracellular l-arginine concentrations manyfold higher than the eNOS KM value.
“This finding was rather surprising, as most cells have intracellular l-arginine concentrations manyfold higher than the eNOS KM value, and thus, this observation has been termed the “arginine paradox” (12, 797).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [12]
Direct supplementation of l-arginine increases NO production in cells.
“The direct supplementation of l-arginine was shown to increase NO production in cells.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [12]
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- Authors
- Aisaka, K., Gross, S. S., Griffith, O. W., & Levi, R.
- Affiliations
- Cornell University (US)
- Corresponding author
- Levi, Roberto
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 1989-09
- Volume
- 163
- Issue
- 2
- Pages
- 710-717
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2006890214
- Cited by
- 123
- References
- 22
- Citations by year
- 2025: 1 · 2021: 1 · 2018: 2 · 2015: 1 · 2014: 2
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL37407, HL18828, HL-34215)
- 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, acetylcholine, nitric oxide, endothelium-derived relaxing factor, systemic vasodilatation, hypotensive response, norepinephrine-induced hypertension, guinea pig, nitric oxide synthase
- MeSH terms
- Acetylcholine, Animals, Arginine, Biological Availability, Blood Pressure, Depression, Chemical, Guinea Pigs, Male, Nitric Oxide, Time Factors, Vasodilation, omega-N-Methylarginine
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