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The aim of this study was to determine the contribution of IP and EP<jats:sub>3<\/jats:sub> prostanoid receptors to prostacyclin mimetic iloprost\u2010mediated responses, whether K<jats:sub>V<\/jats:sub>7.1\u20135 channels represent downstream targets of selective prostacyclin\u2010IP\u2010receptor agonist MRE\u2010269 and the impact of the oestrus cycle on vascular reactivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Within second\u2010order mesenteric arteries from male and female Wistar rats, we determined (1) relative mRNA transcripts for EP<jats:sub>1\u20134<\/jats:sub> (<jats:italic>Ptger<\/jats:italic><jats:sub><jats:italic>1\u20134<\/jats:italic><\/jats:sub>), IP (<jats:italic>Ptgi<\/jats:italic>) and TXA<jats:sub>2<\/jats:sub> (<jats:italic>Tbxa<\/jats:italic>) prostanoid receptors via RT\u2010qPCR; (2) the effect of iloprost, MRE\u2010269, isoprenaline and ML277 on precontracted arterial tone in the presence of inhibitors of prostanoid receptors, potassium channels and the molecular interference of K<jats:sub>V<\/jats:sub>7.1 via wire\u2010myograph; (3) oestrus cycle stage via histological changes in cervical cell preparations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Iloprost evoked a biphasic response in male mesenteric arteries, at concentrations \u2264100\u2009nmol\u00b7L<jats:sup>\u22121<\/jats:sup> relaxing, then contracting the vessel at concentration \u2265300\u2009nmol\u00b7L<jats:sup>\u22121<\/jats:sup>, a process attributed to IP and EP<jats:sub>3<\/jats:sub> receptors respectively. Secondary contraction was absent in the females, which was associated with a reduction in <jats:italic>Ptger3<\/jats:italic>. Pharmacological inhibition and molecular interference of K<jats:sub>V<\/jats:sub>7.1 significantly attenuated relaxations produced by the selective IP receptor agonist MRE\u2010269 in male and female Wistar in dioestrus\/metoestrus, but not pro\u2010oestrus\/oestrus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Stark sexual dimorphisms in iloprost\u2010mediated vasoactive responses are present within mesenteric arteries. K<jats:sub>V<\/jats:sub>7.1 is implicated in IP receptor\u2010mediated vasorelaxation and is impaired by the oestrus cycle.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15722","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T11:34:41Z","timestamp":1636716881000},"page":"1338-1352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Sexual dimorphism in prostacyclin\u2010mimetic responses within rat mesenteric arteries: A novel role for K<sub>V<\/sub>7.1 in shaping IP receptor\u2010mediated relaxation"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3796-6090","authenticated-orcid":false,"given":"Samuel N.","family":"Baldwin","sequence":"first","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute St. George's University  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2164-103X","authenticated-orcid":false,"given":"Elizabeth A.","family":"Forrester","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute St. George's University  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1983-2574","authenticated-orcid":false,"given":"Lauren","family":"McEwan","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute St. George's University  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0603-0492","authenticated-orcid":false,"given":"Iain A.","family":"Greenwood","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute St. George's University  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000449060"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15538"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15539"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.215772"},{"key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphys.2020.598779","article-title":"KV7 channel expression and function within rat mesenteric endothelial cells","volume":"11","author":"Baldwin S. 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