{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:17:36Z","timestamp":1779895056506,"version":"3.53.1"},"reference-count":38,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:p>The mechanisms through which p38 mitogen-activated protein kinase (p38 MAPK) is involved in smooth muscle contraction remain largely unresolved. We examined the role of p38 MAPK in prostaglandin F<jats:sub>2\u03b1<\/jats:sub>(PGF<jats:sub>2\u03b1<\/jats:sub>)-induced vasoconstriction and in hypoxic pulmonary vasoconstriction (HPV) of rat small intrapulmonary arteries (IPA). The p38 MAPK inhibitors SB-203580 and SB-202190 strongly inhibited PGF<jats:sub>2\u03b1<\/jats:sub>-induced vasoconstriction, with IC<jats:sub>50<\/jats:sub>s of 1.6 and 1.2 \u03bcM, whereas the inactive analog SB-202474 was \u223c30-fold less potent. Both transient and sustained phases of HPV were suppressed by SB-203580, but not by SB-202474 (both 2 \u03bcM). Western blot analysis revealed that PGF<jats:sub>2\u03b1<\/jats:sub>(20 \u03bcM) increased phosphorylation of p38 MAPK and of heat shock protein 27 (HSP27), and this was abolished by SB-203580 but not by SB-202474 (both 2 \u03bcM). Endothelial denudation or blockade of endothelial nitric oxide (NO) synthase with N<jats:sup>\u03c9<\/jats:sup>-nitro-l-arginine methyl ester (l-NAME) significantly suppressed the relaxation of PGF<jats:sub>2\u03b1<\/jats:sub>-constricted IPA by SB-203580, but not by SB-202474. Similarly, the inhibition of HPV by SB-203580 was prevented by prior treatment with l-NAME. SB-203580 (2 \u03bcM), but not SB-202474, enhanced relaxation-induced by the NO donor S-nitroso- N-acetylpenicillamine (SNAP) in endothelium-denuded IPA constricted with PGF<jats:sub>2\u03b1<\/jats:sub>. In \u03b1-toxin-permeabilized IPA, SB-203580-induced relaxation occurred in the presence but not the absence of the NO donor sodium nitroprusside (SNP); SB-202474 was without effect even in the presence of SNP. In intact IPA, neither PGF<jats:sub>2\u03b1<\/jats:sub>- nor SNAP-mediated changes in cytosolic free Ca<jats:sup>2+<\/jats:sup>were affected by SB-203580. We conclude that p38 MAPK contributes to PGF<jats:sub>2\u03b1<\/jats:sub>- and hypoxia-induced constriction of rat IPA primarily by antagonizing the underlying Ca<jats:sup>2+<\/jats:sup>-desensitizing actions of NO.<\/jats:p>","DOI":"10.1152\/ajplung.00094.2005","type":"journal-article","created":{"date-parts":[[2005,7,30]],"date-time":"2005-07-30T00:24:08Z","timestamp":1122683048000},"page":"L1039-L1048","source":"Crossref","is-referenced-by-count":8,"title":["Modulation of PGF<sub>2\u03b1<\/sub>- and hypoxia-induced contraction of rat intrapulmonary artery by p38 MAPK inhibition: a nitric oxide-dependent mechanism"],"prefix":"10.1152","volume":"289","author":[{"given":"Greg A.","family":"Knock","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anushika S.","family":"De Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir A.","family":"Snetkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Siow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin D.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuya","family":"Shiraishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy P. 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