{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T10:27:18Z","timestamp":1763807238744},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T00:00:00Z","timestamp":1468540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Progranulin (<jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content>) is a novel adipocytokine with anti\u2010inflammatory effects in vascular cells. The aim of this study was to clarify the effects of <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> on reactivity of isolated blood vessel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Isometric contraction of rat isolated superior mesenteric artery was measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pre\u2010treatment with <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> (10\u2013100\u00a0ng\u00a0mL<jats:sup>\u22121<\/jats:sup>, 30\u00a0min) had no effect on noradrenaline\u2010 or 5\u2010hydroxytriptamine\u2010induced contraction. On the other hand, pre\u2010treatment with <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> (100\u00a0ng\u00a0mL<jats:sup>\u22121<\/jats:sup>) augmented acetylcholine (<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h; 30\u00a0n<jats:sc>m<\/jats:sc>)\u2010induced endothelium\u2010dependent relaxation. Pre\u2010treatment with <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> (100\u00a0ng\u00a0mL<jats:sup>\u22121<\/jats:sup>) augmented <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h (10\u00a0<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>)\u2010induced nitric oxide (<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>)\u2010mediated relaxation in the presence of indomethacin (10\u00a0<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>), a cyclooxygenase inhibitor, and tetraethyl ammonium (10\u00a0m<jats:sc>m<\/jats:sc>), a non\u2010selective potassium channel blocker. In contrast, pre\u2010treatment with <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> (100\u00a0ng\u00a0mL<jats:sup>\u22121<\/jats:sup>) had no effect on <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h\u2010induced endothelium\u2010derived hyperpolarizing factor\u2010mediated relaxation. Pre\u2010treatment with <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> (100\u00a0ng\u00a0mL<jats:sup>\u22121<\/jats:sup>) had no effect on <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h (10\u00a0<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>, 1\u00a0min)\u2010induced endothelial <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> synthase phosphorylation (at Ser1177) as determined by Western blotting. Pre\u2010treatment with <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> (100\u00a0ng\u00a0mL<jats:sup>\u22121<\/jats:sup>) augmented an <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> donor, sodium nitroprusside (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>; 30\u00a0n<jats:sc>m<\/jats:sc>\u20131\u00a0<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>)\u2010 but not a membrane\u2010permeable <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content> analogue, 8\u2010bromo\u2010<jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>\u2010induced relaxation. In the presence of 3\u2010isobutyl\u20101\u2010methylxanthine (100\u00a0<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>), a phosphodiesterase inhibitor, pre\u2010treatment with <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> (100\u00a0ng\u00a0mL<jats:sup>\u22121<\/jats:sup>) increased <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content> (30\u00a0n<jats:sc>m<\/jats:sc>, 5\u00a0min)\u2010induced <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content> production as determined by enzyme immunoassay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We for the first time demonstrate that <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> augments <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h\u2010induced <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\u2010mediated relaxation through the increases of <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content> production in smooth muscle. These results indicate <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> as a possible pharmacotherapeutic target against cardiovascular diseases including obesity\u2010related hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12739","type":"journal-article","created":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T21:06:34Z","timestamp":1466629594000},"page":"781-789","source":"Crossref","is-referenced-by-count":11,"title":["Adipocytokine, progranulin, augments acetylcholine\u2010induced nitric oxide\u2010mediated relaxation through the increases of <scp>cGMP<\/scp> production in rat isolated mesenteric artery"],"prefix":"10.1111","volume":"219","author":[{"given":"K.","family":"Kazama","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Pharmacology School of Veterinary Medicine Kitasato University Towada Aomori 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