Acetylcholine protects mesenteric arteries against hypoxia/reoxygenation injury via inhibiting calcium-sensing receptor
The Ca2+-sensing receptor (CaSR) plays an important role in regulating vascular tone. In the present study, we investigated the positive effects of the vagal neurotransmitter acetylcholine by suppressing CaSR activation in mesenteric arteries exposed to hypoxia/reoxygenation (H/R). The artery rings...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-04-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861315000730 |
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| author | Ming Zhao Xi He Yong-Hua Yang Xiao-Jiang Yu Xue-Yuan Bi Yang Yang Man Xu Xing-Zhu Lu Qiang Sun Wei-Jin Zang |
| author_facet | Ming Zhao Xi He Yong-Hua Yang Xiao-Jiang Yu Xue-Yuan Bi Yang Yang Man Xu Xing-Zhu Lu Qiang Sun Wei-Jin Zang |
| author_sort | Ming Zhao |
| collection | DOAJ |
| description | The Ca2+-sensing receptor (CaSR) plays an important role in regulating vascular tone. In the present study, we investigated the positive effects of the vagal neurotransmitter acetylcholine by suppressing CaSR activation in mesenteric arteries exposed to hypoxia/reoxygenation (H/R). The artery rings were exposed to a modified ‘ischemia mimetic’ solution and an anaerobic environment to simulate an H/R model. Our results showed that acetylcholine (10−6 mol/L) significantly reduced the contractions induced by KCl and phenylephrine and enhanced the endothelium-dependent relaxation induced by acetylcholine. Additionally, acetylcholine reduced CaSR mRNA expression and activity when the rings were subjected to 4 h of hypoxia and 12 h of reoxygenation. Notably, the CaSR antagonist NPS2143 significantly reduced the contractions but did not improve the endothelium-dependent relaxation. When a contractile response was achieved with extracellular Ca2+, both acetylcholine and NPS2143 reversed the H/R-induced abnormal vascular vasoconstriction, and acetylcholine reversed the calcimimetic R568-induced abnormal vascular vasoconstriction in the artery rings. In conclusion, this study suggests that acetylcholine ameliorates the dysfunctional vasoconstriction of the arteries after H/R, most likely by decreasing CaSR expression and activity, thereby inhibiting the increase in intracellular calcium concentration. Our findings may be indicative of a novel mechanism underlying ACh-induced vascular protection. |
| first_indexed | 2024-12-16T08:28:10Z |
| format | Article |
| id | doaj.art-ba902d49b6ad4b1582dee676ee0cd0ba |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-16T08:28:10Z |
| publishDate | 2015-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-ba902d49b6ad4b1582dee676ee0cd0ba2022-12-21T22:37:57ZengElsevierJournal of Pharmacological Sciences1347-86132015-04-01127448148810.1016/j.jphs.2015.03.011Acetylcholine protects mesenteric arteries against hypoxia/reoxygenation injury via inhibiting calcium-sensing receptorMing Zhao0Xi He1Yong-Hua Yang2Xiao-Jiang Yu3Xue-Yuan Bi4Yang Yang5Man Xu6Xing-Zhu Lu7Qiang Sun8Wei-Jin Zang9Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR ChinaDepartment of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR ChinaDepartment of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR ChinaDepartment of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR ChinaDepartment of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR ChinaDepartment of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR ChinaDepartment of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR ChinaDepartment of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR ChinaDepartment of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR ChinaDepartment of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR ChinaThe Ca2+-sensing receptor (CaSR) plays an important role in regulating vascular tone. In the present study, we investigated the positive effects of the vagal neurotransmitter acetylcholine by suppressing CaSR activation in mesenteric arteries exposed to hypoxia/reoxygenation (H/R). The artery rings were exposed to a modified ‘ischemia mimetic’ solution and an anaerobic environment to simulate an H/R model. Our results showed that acetylcholine (10−6 mol/L) significantly reduced the contractions induced by KCl and phenylephrine and enhanced the endothelium-dependent relaxation induced by acetylcholine. Additionally, acetylcholine reduced CaSR mRNA expression and activity when the rings were subjected to 4 h of hypoxia and 12 h of reoxygenation. Notably, the CaSR antagonist NPS2143 significantly reduced the contractions but did not improve the endothelium-dependent relaxation. When a contractile response was achieved with extracellular Ca2+, both acetylcholine and NPS2143 reversed the H/R-induced abnormal vascular vasoconstriction, and acetylcholine reversed the calcimimetic R568-induced abnormal vascular vasoconstriction in the artery rings. In conclusion, this study suggests that acetylcholine ameliorates the dysfunctional vasoconstriction of the arteries after H/R, most likely by decreasing CaSR expression and activity, thereby inhibiting the increase in intracellular calcium concentration. Our findings may be indicative of a novel mechanism underlying ACh-induced vascular protection.http://www.sciencedirect.com/science/article/pii/S1347861315000730AcetylcholineHypoxia/reoxygenationCalcium-sensing receptorVascular functionMesenteric artery |
| spellingShingle | Ming Zhao Xi He Yong-Hua Yang Xiao-Jiang Yu Xue-Yuan Bi Yang Yang Man Xu Xing-Zhu Lu Qiang Sun Wei-Jin Zang Acetylcholine protects mesenteric arteries against hypoxia/reoxygenation injury via inhibiting calcium-sensing receptor Journal of Pharmacological Sciences Acetylcholine Hypoxia/reoxygenation Calcium-sensing receptor Vascular function Mesenteric artery |
| title | Acetylcholine protects mesenteric arteries against hypoxia/reoxygenation injury via inhibiting calcium-sensing receptor |
| title_full | Acetylcholine protects mesenteric arteries against hypoxia/reoxygenation injury via inhibiting calcium-sensing receptor |
| title_fullStr | Acetylcholine protects mesenteric arteries against hypoxia/reoxygenation injury via inhibiting calcium-sensing receptor |
| title_full_unstemmed | Acetylcholine protects mesenteric arteries against hypoxia/reoxygenation injury via inhibiting calcium-sensing receptor |
| title_short | Acetylcholine protects mesenteric arteries against hypoxia/reoxygenation injury via inhibiting calcium-sensing receptor |
| title_sort | acetylcholine protects mesenteric arteries against hypoxia reoxygenation injury via inhibiting calcium sensing receptor |
| topic | Acetylcholine Hypoxia/reoxygenation Calcium-sensing receptor Vascular function Mesenteric artery |
| url | http://www.sciencedirect.com/science/article/pii/S1347861315000730 |
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