Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP
Open accessAbstract
The present study investigates the hypothesis that endothelium-dependent relaxation of vascular smooth muscle may be mediated through the formation of cGMP. Relaxation of the rat thoracic aorta to acetylcholine, histamine, and Ca++ ionophore A23187 was associated with increased levels of cGMP in a time- and concentration-dependent manner, whereas cAMP levels were unaltered. Removal of the endothelium prevented relaxation to these agents and prevented the increased levels of cGMP. Removal of the endothelium after exposure to acetylcholine only partially decreased the elevated levels of cGMP, suggesting that the changes in cGMP occurred within the smooth muscle cells. Eicosatetraynoic acid, an inhibitor of lipoxygenase and cyclooxygenase, and quinacrine, an inhibitor of phospholipase, prevented and reversed acetylcholine-induced relaxation, respectively, and inhibited acetylcholine-induced increased levels of cGMP. In contrast, sodium nitroprusside-induced relaxation and increased levels of cGMP were independent of the presence of the endothelium, exposure to eicosatetraynoic acid, and quinacrine. The present results support the hypothesis that vascular smooth muscle relaxation induced by some agents is dependent on the presence of the endothelium and is mediated through the formation of an endothelial factor that increases cGMP levels in smooth muscle.
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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 [97]
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- Authors
- Rapoport, R. M., & Murad, F.
- Affiliations
- VA Palo Alto Health Care System (US)
- Venue
- Circulation Research
- Published
- 1983-03
- Volume
- 52
- Issue
- 3
- Pages
- 352-357
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2077798575
- Cited by
- 928
- References
- 23
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 9 · 2019: 13 · 2018: 11 · 2017: 9 · 2016: 9 · 2015: 11 · 2014: 16 · 2013: 5 · 2012: 12
- FWCI
- 31.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01am030787-05)
- 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 › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- endothelium-dependent relaxation, cyclic GMP, thoracic aorta, acetylcholine, histamine, A23187, eicosatetraynoic acid, quinacrine, sodium nitroprusside, vascular smooth muscle, endothelium, lipoxygenase, phospholipase inhibition, cyclic AMP
- MeSH terms
- Calcimycin, Acetylcholine, Animals, Aorta, Thoracic, Arachidonic Acids, Cyclic GMP, Histamine, Male, Muscle Relaxation, Muscle, Smooth, Vascular, Nitroprusside, Quinacrine, Rats, Inbred Strains, Rats
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