Endothelium-dependent relaxation in rat aorta may be mediated through cyclic GMP-dependent protein phosphorylation
Abstract
The action of some vascular smooth muscle relaxants depends on the presence of the endothelium. We have recently shown that relaxation may be mediated through the formation of cyclic GMP. The nitrovasodilators are another class of relaxants which exert their effects through the formation of cyclic GMP, although their relaxation is independent of the presence of the endothelium. Their relaxant properties seem to depend on free radical formation--specifically, the formation of nitric oxide. The NO-induced smooth muscle relaxation is proposed to occur through activation of guanylate cyclase and the formation of cyclic GMP. Protein phosphorylation is thought to be a common event in the pathway for many biological phenomena. Moreover, sodium nitroprusside and 8-bromo cyclic GMP induce similar patterns of protein phosphorylation in intact rat thoracic aorta. Here we report that the patterns of protein phosphorylation induced by the endothelium-dependent vasodilators and nitrovasodilators were identical. Incorporation of 32P into myosin light chain was decreased by both classes of agents. Removal of the endothelium abolished the changes in phosphorylation with the endothelium-dependent vasodilator (acetylcholine), but not those with the nitrovasodilator (sodium nitroprusside). These results suggest that endothelium-dependent vasodilators and nitrovasodilators induce relaxation through cyclic GMP-dependent protein phosphorylation and dephosphorylation of myosin light chain.
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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 [96]
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- Authors
- Rapoport, R. M., Draznin, M. B., & Murad, F.
- Affiliations
- Stanford Medicine (US)
- Venue
- Nature
- Published
- 1983-11
- Volume
- 306
- Issue
- 5939
- Pages
- 174-176
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2016204376
- Cited by
- 631
- References
- 20
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 13 · 2022: 8 · 2021: 10 · 2020: 8 · 2019: 17 · 2018: 9 · 2017: 15 · 2016: 8 · 2015: 9 · 2014: 24 · 2013: 7 · 2012: 18
- FWCI
- 12.71
- 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 › Molecular Biology › Phosphodiesterase function and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- endothelium-dependent relaxation, cyclic GMP, protein phosphorylation, myosin light chain dephosphorylation, nitric oxide, nitrovasodilators, sodium nitroprusside, acetylcholine, guanylate cyclase, vasorelaxation
- MeSH terms
- Acetylcholine, Animals, Aorta, Endothelium, Cyclic GMP, Isoelectric Point, Male, Molecular Weight, Muscle Contraction, Muscle Proteins, Muscle Relaxation, Muscle, Smooth, Vascular, Myosins, Nitroprusside, Phosphoproteins, Rats
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