Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Min, Li, Chunshu, He, Chunxia, Cui, Yiqin, Li, Yuan, Ma, Ying, Cheng, Jun, Wen, Jing, Li, Pengyun, Yang, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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
_version_ 1784817430571253760
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
work_keys_str_mv AT zhangmin thromboxaneinducedcontractileresponseofmesentericarteriolesisdiminishedintheolderratsandtheolderhypertensiverats
AT lichunshu thromboxaneinducedcontractileresponseofmesentericarteriolesisdiminishedintheolderratsandtheolderhypertensiverats
AT hechunxia thromboxaneinducedcontractileresponseofmesentericarteriolesisdiminishedintheolderratsandtheolderhypertensiverats
AT cuiyiqin thromboxaneinducedcontractileresponseofmesentericarteriolesisdiminishedintheolderratsandtheolderhypertensiverats
AT liyuan thromboxaneinducedcontractileresponseofmesentericarteriolesisdiminishedintheolderratsandtheolderhypertensiverats
AT maying thromboxaneinducedcontractileresponseofmesentericarteriolesisdiminishedintheolderratsandtheolderhypertensiverats
AT chengjun thromboxaneinducedcontractileresponseofmesentericarteriolesisdiminishedintheolderratsandtheolderhypertensiverats
AT wenjing thromboxaneinducedcontractileresponseofmesentericarteriolesisdiminishedintheolderratsandtheolderhypertensiverats
AT lipengyun thromboxaneinducedcontractileresponseofmesentericarteriolesisdiminishedintheolderratsandtheolderhypertensiverats
AT yangyan thromboxaneinducedcontractileresponseofmesentericarteriolesisdiminishedintheolderratsandtheolderhypertensiverats