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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602936/ https://www.ncbi.nlm.nih.gov/pubmed/36313372 http://dx.doi.org/10.3389/fphar.2022.1019511 |
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author | Zhang, Min Li, Chunshu He, Chunxia Cui, Yiqin Li, Yuan Ma, Ying Cheng, Jun Wen, Jing Li, Pengyun Yang, Yan |
author_facet | Zhang, Min Li, Chunshu He, Chunxia Cui, Yiqin Li, Yuan Ma, Ying Cheng, Jun Wen, Jing Li, Pengyun Yang, Yan |
author_sort | Zhang, Min |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9602936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96029362022-10-27 Thromboxane-induced contractile response of mesenteric arterioles is diminished in the older rats and the older hypertensive rats Zhang, Min Li, Chunshu He, Chunxia Cui, Yiqin Li, Yuan Ma, Ying Cheng, Jun Wen, Jing Li, Pengyun Yang, Yan Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2022-10-12 /pmc/articles/PMC9602936/ /pubmed/36313372 http://dx.doi.org/10.3389/fphar.2022.1019511 Text en Copyright © 2022 Zhang, Li, He, Cui, Li, Ma, Cheng, Wen, Li and Yang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Zhang, Min Li, Chunshu He, Chunxia Cui, Yiqin Li, Yuan Ma, Ying Cheng, Jun Wen, Jing Li, Pengyun Yang, Yan Thromboxane-induced contractile response of mesenteric arterioles is diminished in the older rats and the older hypertensive rats |
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 | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602936/ https://www.ncbi.nlm.nih.gov/pubmed/36313372 http://dx.doi.org/10.3389/fphar.2022.1019511 |
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