Safranal Induces Vasorelaxation by Inhibiting Ca<sup>2+</sup> Influx and Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger in Isolated Rat Aortic Rings
<b>Introduction:</b> 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. <b>Methods:</b>...
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MDPI AG
2022-06-01
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| Online Access: | https://www.mdpi.com/1420-3049/27/13/4228 |
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| author | Noor Nadhim Al-Saigh Shtaywy Abdalla |
| author_facet | Noor Nadhim Al-Saigh Shtaywy Abdalla |
| author_sort | Noor Nadhim Al-Saigh |
| collection | DOAJ |
| description | <b>Introduction:</b> 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. <b>Methods:</b> 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<sub>2</sub> 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<sup>2+</sup> influx, phenylephrine and CaCl<sub>2</sub> 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<sup>+</sup>-K<sup>+</sup> ATPase inhibitor, was studied to explore the contribution of Na<sup>+</sup>/Ca<sup>2+</sup> exchanger to this vasodilation. <b>Results:</b> 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<sub>2</sub> in Ca<sup>2+</sup>-free depolarizing buffer. Safranal also relaxed contractions induced by ouabain, but pretreatment with safranal totally abolished the development of ouabain contractions. <b>Discussion/Conclusion:</b> Inhibition of Na<sup>+</sup>-K<sup>+</sup> ATPase by ouabain leads to the accumulation of Na<sup>+</sup> intracellularly, forcing the Na<sup>+</sup>/Ca<sup>2+</sup> 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<sup>+</sup>/Ca<sup>2+</sup> exchanger. We conclude that safranal vasodilation is mediated by the inhibition of calcium influx from extracellular space through L-type Ca<sup>2+</sup> channels and by the inhibition of the Na<sup>+</sup>/Ca<sup>2+</sup> exchanger. |
| first_indexed | 2024-03-09T10:26:18Z |
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| last_indexed | 2024-03-09T10:26:18Z |
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| spelling | doaj.art-32fd7956cd834fe6bee50825f56492f92023-12-01T21:36:38ZengMDPI AGMolecules1420-30492022-06-012713422810.3390/molecules27134228Safranal Induces Vasorelaxation by Inhibiting Ca<sup>2+</sup> Influx and Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger in Isolated Rat Aortic RingsNoor Nadhim Al-Saigh0Shtaywy Abdalla1Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, JordanDepartment of Biological Sciences, School of Science, The University of Jordan, Amman 11942, Jordan<b>Introduction:</b> 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. <b>Methods:</b> 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<sub>2</sub> 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<sup>2+</sup> influx, phenylephrine and CaCl<sub>2</sub> 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<sup>+</sup>-K<sup>+</sup> ATPase inhibitor, was studied to explore the contribution of Na<sup>+</sup>/Ca<sup>2+</sup> exchanger to this vasodilation. <b>Results:</b> 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<sub>2</sub> in Ca<sup>2+</sup>-free depolarizing buffer. Safranal also relaxed contractions induced by ouabain, but pretreatment with safranal totally abolished the development of ouabain contractions. <b>Discussion/Conclusion:</b> Inhibition of Na<sup>+</sup>-K<sup>+</sup> ATPase by ouabain leads to the accumulation of Na<sup>+</sup> intracellularly, forcing the Na<sup>+</sup>/Ca<sup>2+</sup> 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<sup>+</sup>/Ca<sup>2+</sup> exchanger. We conclude that safranal vasodilation is mediated by the inhibition of calcium influx from extracellular space through L-type Ca<sup>2+</sup> channels and by the inhibition of the Na<sup>+</sup>/Ca<sup>2+</sup> exchanger.https://www.mdpi.com/1420-3049/27/13/4228Ca<sup>2+</sup> influxNa<sup>+</sup>/Ca<sup>2+</sup> exchangerouabainsafranalvasodilation |
| spellingShingle | Noor Nadhim Al-Saigh Shtaywy Abdalla Safranal Induces Vasorelaxation by Inhibiting Ca<sup>2+</sup> Influx and Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger in Isolated Rat Aortic Rings Molecules Ca<sup>2+</sup> influx Na<sup>+</sup>/Ca<sup>2+</sup> exchanger ouabain safranal vasodilation |
| title | Safranal Induces Vasorelaxation by Inhibiting Ca<sup>2+</sup> Influx and Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger in Isolated Rat Aortic Rings |
| title_full | Safranal Induces Vasorelaxation by Inhibiting Ca<sup>2+</sup> Influx and Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger in Isolated Rat Aortic Rings |
| title_fullStr | Safranal Induces Vasorelaxation by Inhibiting Ca<sup>2+</sup> Influx and Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger in Isolated Rat Aortic Rings |
| title_full_unstemmed | Safranal Induces Vasorelaxation by Inhibiting Ca<sup>2+</sup> Influx and Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger in Isolated Rat Aortic Rings |
| title_short | Safranal Induces Vasorelaxation by Inhibiting Ca<sup>2+</sup> Influx and Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger in Isolated Rat Aortic Rings |
| title_sort | safranal induces vasorelaxation by inhibiting ca sup 2 sup influx and na sup sup ca sup 2 sup exchanger in isolated rat aortic rings |
| topic | Ca<sup>2+</sup> influx Na<sup>+</sup>/Ca<sup>2+</sup> exchanger ouabain safranal vasodilation |
| url | https://www.mdpi.com/1420-3049/27/13/4228 |
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