Thromboxane-induced contractile response of mesenteric arterioles is diminished in the older rats and the older hypertensive rats
Nearly all physiological processes are controlled at some level by G-protein-coupled receptor (GPCR) signaling activity. The thromboxane A2 (TXA2) receptor (TP) is a member of the GPCR family. The ultimate effect of TP receptor activation depends on the availability of specific G proteins, which in...
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1019511/full |
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| author | Min Zhang Chunshu Li Chunxia He Yiqin Cui Yuan Li Ying Ma Jun Cheng Jing Wen Pengyun Li Yan Yang |
| author_facet | Min Zhang Chunshu Li Chunxia He Yiqin Cui Yuan Li Ying Ma Jun Cheng Jing Wen Pengyun Li Yan Yang |
| author_sort | Min Zhang |
| collection | DOAJ |
| description | Nearly all physiological processes are controlled at some level by G-protein-coupled receptor (GPCR) signaling activity. The thromboxane A2 (TXA2) receptor (TP) is a member of the GPCR family. The ultimate effect of TP receptor activation depends on the availability of specific G proteins, which in turn depend on the cell type, tissue, and disease state. However, the roles of the TXA2-TP signaling pathway executed under disease states are poorly defined. In this study, 16-week-spontaneously hypertensive rats (SHR), the 18-month-SHR (OldSHR), and the age-matched Wistar-Kyoto (WKY) rats were used to study the vasoconstriction of mesenteric resistance artery induced by TP-specific agonist, U-46619. Vasoconstriction induced by U-46619 was significantly attenuated in OldWKY and OldSHR rats, and mesenteric arteries with impaired response to U-46619 responded strongly to the adrenergic receptor agonist, phenylephrine. Similar vascular responses to U-46619 were obtained in endothelium-denuded mesenteric arteries. Accordingly, the expression of TP membrane proteins in mesenteric vessels was decreased, and the endogenous TP competitor, 8, 9-EET, in serum was increased, which was partly responsible for the decreased vascular reactivity of U-46619. Decreased TP membrane expression was associated with TP endocytosis, which involved actin cytoskeletal remodeling, including increased ratio of F-actin/G-actin in OldWKY and OldSHR rats. Hence, we studied the effects of TXA2 and its receptors on blood vessels and found that the TXA2-TP prostaglandin signaling pathway was impaired in older adults, which would facilitate the creation of “precision therapeutics” that possess selective efficacy in diseases. |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T17:03:52Z |
| publishDate | 2022-10-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-aedc8d2c28894fe5a473971d9f479ef52022-12-22T04:13:06ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.10195111019511Thromboxane-induced contractile response of mesenteric arterioles is diminished in the older rats and the older hypertensive ratsMin ZhangChunshu LiChunxia HeYiqin CuiYuan LiYing MaJun ChengJing WenPengyun LiYan YangNearly all physiological processes are controlled at some level by G-protein-coupled receptor (GPCR) signaling activity. The thromboxane A2 (TXA2) receptor (TP) is a member of the GPCR family. The ultimate effect of TP receptor activation depends on the availability of specific G proteins, which in turn depend on the cell type, tissue, and disease state. However, the roles of the TXA2-TP signaling pathway executed under disease states are poorly defined. In this study, 16-week-spontaneously hypertensive rats (SHR), the 18-month-SHR (OldSHR), and the age-matched Wistar-Kyoto (WKY) rats were used to study the vasoconstriction of mesenteric resistance artery induced by TP-specific agonist, U-46619. Vasoconstriction induced by U-46619 was significantly attenuated in OldWKY and OldSHR rats, and mesenteric arteries with impaired response to U-46619 responded strongly to the adrenergic receptor agonist, phenylephrine. Similar vascular responses to U-46619 were obtained in endothelium-denuded mesenteric arteries. Accordingly, the expression of TP membrane proteins in mesenteric vessels was decreased, and the endogenous TP competitor, 8, 9-EET, in serum was increased, which was partly responsible for the decreased vascular reactivity of U-46619. Decreased TP membrane expression was associated with TP endocytosis, which involved actin cytoskeletal remodeling, including increased ratio of F-actin/G-actin in OldWKY and OldSHR rats. Hence, we studied the effects of TXA2 and its receptors on blood vessels and found that the TXA2-TP prostaglandin signaling pathway was impaired in older adults, which would facilitate the creation of “precision therapeutics” that possess selective efficacy in diseases.https://www.frontiersin.org/articles/10.3389/fphar.2022.1019511/fullaging-related vascular remodelingmesenteric arteryU-46619vasoconstrictionTXA2-TP prostaglandin signaling pathway |
| spellingShingle | Min Zhang Chunshu Li Chunxia He Yiqin Cui Yuan Li Ying Ma Jun Cheng Jing Wen Pengyun Li Yan Yang Thromboxane-induced contractile response of mesenteric arterioles is diminished in the older rats and the older hypertensive rats Frontiers in Pharmacology aging-related vascular remodeling mesenteric artery U-46619 vasoconstriction TXA2-TP prostaglandin signaling pathway |
| title | Thromboxane-induced contractile response of mesenteric arterioles is diminished in the older rats and the older hypertensive rats |
| title_full | Thromboxane-induced contractile response of mesenteric arterioles is diminished in the older rats and the older hypertensive rats |
| title_fullStr | Thromboxane-induced contractile response of mesenteric arterioles is diminished in the older rats and the older hypertensive rats |
| title_full_unstemmed | Thromboxane-induced contractile response of mesenteric arterioles is diminished in the older rats and the older hypertensive rats |
| title_short | Thromboxane-induced contractile response of mesenteric arterioles is diminished in the older rats and the older hypertensive rats |
| title_sort | thromboxane induced contractile response of mesenteric arterioles is diminished in the older rats and the older hypertensive rats |
| topic | aging-related vascular remodeling mesenteric artery U-46619 vasoconstriction TXA2-TP prostaglandin signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1019511/full |
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