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Therefore, a better understanding of the prostaglandin system and characterising the effects of mPGES\u20101 inhibition and concomitant reduction of PGE<jats:sub>2<\/jats:sub> in vascular beds are of interest.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The effects of mPGES\u20101 inhibition on constriction and relaxation of resistance arteries (diameter: 100\u2013400\u2009\u03bcm) from patients with end stage kidney disease (ESKD) and controls (Non\u2010ESKD) were studied using wire\u2010myography in combination with immunological and mass\u2010spectrometry based analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Inhibition of mPGES\u20101 in arteries from ESKD patients and Non\u2010ESKD controls significantly reduced adrenergic vasoconstriction, which was unaffected by the COX\u20102 inhibitors NS\u2010398 and Etoricoxib, or by the COX\u20101\/COX\u20102 inhibitor Indomethacin tested in Non\u2010ESKD controls. However, a significant increase of acetylcholine\u2010induced dilatation was observed for mPGES\u20101 inhibition. In IL\u20101\u03b2 treated arteries, inhibition of mPGES\u20101 significantly reduced PGE<jats:sub>2<\/jats:sub> levels while PGI<jats:sub>2<\/jats:sub> levels remained unchanged. In contrast, COX\u20102 inhibition blocked the formation of both prostaglandins. Blockade of PGI<jats:sub>2<\/jats:sub> signalling with an IP receptor antagonist did not restore the reduced adrenergic constriction, neither did blocking PGE<jats:sub>2<\/jats:sub>\u2010EP4 or signalling through PPAR\u03b3. A biphasic effect was observed for PGE<jats:sub>2<\/jats:sub>, inducing dilatation at nanomolar and constriction at micromolar concentrations. Immunohistochemistry demonstrated expression of mPGES\u20101, COX\u20101, PGIS, weak expression for COX\u20102, as well as receptor expression for PGE<jats:sub>2<\/jats:sub> (EP1\u20134), thromboxane (TP) and PGI<jats:sub>2<\/jats:sub> (IP) in ESKD and Non\u2010ESKD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrates vasodilating effects following mPGES\u20101 inhibition in human microvasculature and suggests that several pathways besides shunting to PGI<jats:sub>2<\/jats:sub> are involved.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15729","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T07:29:16Z","timestamp":1636702156000},"page":"1433-1449","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of microsomal prostaglandin E synthase\u20101 inhibition on resistance artery tone in patients with end stage kidney disease"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6041-6401","authenticated-orcid":false,"given":"Julia","family":"Steinmetz\u2010Sp\u00e4h","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet &amp; Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samsul","family":"Arefin","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Larsson","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet &amp; Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jabin","family":"Jahan","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet &amp; Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neja","family":"Mudrovcic","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Wennberg","sequence":"additional","affiliation":[{"name":"Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology Karolinska University Hospital, Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Stenvinkel","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Korotkova","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet &amp; Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Kublickiene","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per\u2010Johan","family":"Jakobsson","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet &amp; Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,2,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42506-018-0005-2"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(99)00164-X"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.011591"},{"issue":"1","key":"e_1_2_12_5_1","first-page":"S27","article-title":"THE CONCISE GUIDE TO PHARMACOLOGY 2021\/22: G protein\u2010coupled receptors","volume":"178","author":"Alexander S. 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