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Safranal Induces Vasorelaxation by Inhibiting Ca(2+) Influx and Na(+)/Ca(2+) Exchanger in Isolated Rat Aortic Rings
Introduction: Safranal, which endows saffron its unique aroma, causes vasodilatation and has a hypotensive effect in animal studies, but the mechanisms of these effects are unknown. In this study, we investigated the mechanisms of safranal vasodilation. Methods: Isolated rat endothelium-intact or -d...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268204/ https://www.ncbi.nlm.nih.gov/pubmed/35807473 http://dx.doi.org/10.3390/molecules27134228 |
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author | Al-Saigh, Noor Nadhim Abdalla, Shtaywy |
author_facet | Al-Saigh, Noor Nadhim Abdalla, Shtaywy |
author_sort | Al-Saigh, Noor Nadhim |
collection | PubMed |
description | Introduction: Safranal, which endows saffron its unique aroma, causes vasodilatation and has a hypotensive effect in animal studies, but the mechanisms of these effects are unknown. In this study, we investigated the mechanisms of safranal vasodilation. Methods: Isolated rat endothelium-intact or -denuded aortic rings were precontracted with phenylephrine and then relaxed with safranal. To further assess the involvement of nitric oxide, prostaglandins, guanylate cyclase, and phospholipase A(2) in safranal-induced vasodilation, aortic rings were preincubated with L-NAME, indomethacin, methylene blue, or quinacrine, respectively, then precontracted with phenylephrine, and safranal concentration–response curves were established. To explore the effects of safranal on Ca(2+) influx, phenylephrine and CaCl(2) concentration–response curves were established in the presence of safranal. Furthermore, the effect of safranal on aortic rings in the presence of ouabain, a Na(+)-K(+) ATPase inhibitor, was studied to explore the contribution of Na(+)/Ca(2+) exchanger to this vasodilation. Results: Safranal caused vasodilation in endothelium-intact and endothelium-denuded aortic rings. The vasodilation was not eliminated by pretreatment with L-NAME, indomethacin, methylene blue, or quinacrine, indicating the lack of a role for NO/cGMP. Safranal significantly inhibited the maximum contractions induced by phenylephrine, or by CaCl(2) in Ca(2+)-free depolarizing buffer. Safranal also relaxed contractions induced by ouabain, but pretreatment with safranal totally abolished the development of ouabain contractions. Discussion/Conclusion: Inhibition of Na(+)-K(+) ATPase by ouabain leads to the accumulation of Na(+) intracellularly, forcing the Na(+)/Ca(2+) exchanger to work in reverse mode, thus causing a contraction. Inhibition of the development of this contraction by preincubation with safranal indicates that safranal inhibited the Na(+)/Ca(2+) exchanger. We conclude that safranal vasodilation is mediated by the inhibition of calcium influx from extracellular space through L-type Ca(2+) channels and by the inhibition of the Na(+)/Ca(2+) exchanger. |
format | Online Article Text |
id | pubmed-9268204 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92682042022-07-09 Safranal Induces Vasorelaxation by Inhibiting Ca(2+) Influx and Na(+)/Ca(2+) Exchanger in Isolated Rat Aortic Rings Al-Saigh, Noor Nadhim Abdalla, Shtaywy Molecules Article Introduction: Safranal, which endows saffron its unique aroma, causes vasodilatation and has a hypotensive effect in animal studies, but the mechanisms of these effects are unknown. In this study, we investigated the mechanisms of safranal vasodilation. Methods: Isolated rat endothelium-intact or -denuded aortic rings were precontracted with phenylephrine and then relaxed with safranal. To further assess the involvement of nitric oxide, prostaglandins, guanylate cyclase, and phospholipase A(2) in safranal-induced vasodilation, aortic rings were preincubated with L-NAME, indomethacin, methylene blue, or quinacrine, respectively, then precontracted with phenylephrine, and safranal concentration–response curves were established. To explore the effects of safranal on Ca(2+) influx, phenylephrine and CaCl(2) concentration–response curves were established in the presence of safranal. Furthermore, the effect of safranal on aortic rings in the presence of ouabain, a Na(+)-K(+) ATPase inhibitor, was studied to explore the contribution of Na(+)/Ca(2+) exchanger to this vasodilation. Results: Safranal caused vasodilation in endothelium-intact and endothelium-denuded aortic rings. The vasodilation was not eliminated by pretreatment with L-NAME, indomethacin, methylene blue, or quinacrine, indicating the lack of a role for NO/cGMP. Safranal significantly inhibited the maximum contractions induced by phenylephrine, or by CaCl(2) in Ca(2+)-free depolarizing buffer. Safranal also relaxed contractions induced by ouabain, but pretreatment with safranal totally abolished the development of ouabain contractions. Discussion/Conclusion: Inhibition of Na(+)-K(+) ATPase by ouabain leads to the accumulation of Na(+) intracellularly, forcing the Na(+)/Ca(2+) exchanger to work in reverse mode, thus causing a contraction. Inhibition of the development of this contraction by preincubation with safranal indicates that safranal inhibited the Na(+)/Ca(2+) exchanger. We conclude that safranal vasodilation is mediated by the inhibition of calcium influx from extracellular space through L-type Ca(2+) channels and by the inhibition of the Na(+)/Ca(2+) exchanger. MDPI 2022-06-30 /pmc/articles/PMC9268204/ /pubmed/35807473 http://dx.doi.org/10.3390/molecules27134228 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Al-Saigh, Noor Nadhim Abdalla, Shtaywy Safranal Induces Vasorelaxation by Inhibiting Ca(2+) Influx and Na(+)/Ca(2+) Exchanger in Isolated Rat Aortic Rings |
title | Safranal Induces Vasorelaxation by Inhibiting Ca(2+) Influx and Na(+)/Ca(2+) Exchanger in Isolated Rat Aortic Rings |
title_full | Safranal Induces Vasorelaxation by Inhibiting Ca(2+) Influx and Na(+)/Ca(2+) Exchanger in Isolated Rat Aortic Rings |
title_fullStr | Safranal Induces Vasorelaxation by Inhibiting Ca(2+) Influx and Na(+)/Ca(2+) Exchanger in Isolated Rat Aortic Rings |
title_full_unstemmed | Safranal Induces Vasorelaxation by Inhibiting Ca(2+) Influx and Na(+)/Ca(2+) Exchanger in Isolated Rat Aortic Rings |
title_short | Safranal Induces Vasorelaxation by Inhibiting Ca(2+) Influx and Na(+)/Ca(2+) Exchanger in Isolated Rat Aortic Rings |
title_sort | safranal induces vasorelaxation by inhibiting ca(2+) influx and na(+)/ca(2+) exchanger in isolated rat aortic rings |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268204/ https://www.ncbi.nlm.nih.gov/pubmed/35807473 http://dx.doi.org/10.3390/molecules27134228 |
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