{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:15:06Z","timestamp":1753892106645,"version":"3.41.2"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>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 \u201cprecision therapeutics\u201d that possess selective efficacy in diseases.<\/jats:p>","DOI":"10.3389\/fphar.2022.1019511","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T05:21:51Z","timestamp":1665552111000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Thromboxane-induced contractile response of mesenteric arterioles is diminished in the older rats and the older hypertensive rats"],"prefix":"10.3389","volume":"13","author":[{"given":"Min","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunshu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunxia","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiqin","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengyun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3079","DOI":"10.18632\/aging.101646","article-title":"Aging and drug discovery","volume":"10","author":"Bakula","year":"2018","journal-title":"Aging (Albany NY)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1124\/jpet.108.145102","article-title":"Epoxyeicosatrienoic acids function as selective, endogenous antagonists of native thromboxane receptors: Identification of a novel mechanism of vasodilation","volume":"328","author":"Behm","year":"2009","journal-title":"J. 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