{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T01:22:03Z","timestamp":1783128123709,"version":"3.54.6"},"reference-count":35,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:p>Cerebral hypoxia (10 min) followed immediately by ischemia (20 min) (H\/I) impairs cerebrovasodilation in response to hypercapnia and hypotension in the newborn pig; exogenous urokinase plasminogen activator (uPA) potentiates this effect, whereas the blockade of endogenous uPA-mediated vasoactivity prevents it completely. This study investigated the role of integrin \u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>in the uPA-mediated impairment of cerebrovasodilation after H\/I in piglets equipped with a closed cranial window. Pial artery dilation induced by hypercapnia (Pco<jats:sub>2<\/jats:sub>, 75 mmHg) and hypotension (mean arterial blood pressure, decreased by 45%) was blunted after H\/I, reversed to vasconstriction in piglets treated with uPA (10<jats:sup>\u22127<\/jats:sup>M), a concentration observed in cerebrospinal fluid after H\/I, but reverted to a dilation no different than preinsult in piglets administered an anti-\u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>antibody (10 ng\/ml) in addition to uPA (26 \u00b1 1, 9 \u00b1 1, \u221210 \u00b1 3, and 22 \u00b1 3% for hypercapnia before H\/I, after H\/I, after H\/I with uPA, and after H\/I with combined uPA and anti-\u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>antibody, respectively). Responses to isoproterenol were unchanged after H\/I and combined uPA and anti-\u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>antibody. Similar results were obtained for the combined administration of uPA with the \u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>antagonist Arg-Gly-Asp-d-Phe-Val and Arg-Gly-Asp-Ser, but not for the inactive analog Arg-Gly-Asp-Glu-Ser acetate. These data show that the activation of the integrin \u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>contributes to the uPA-mediated impairment of pial artery dilation after H\/I. These data suggest that the inhibition of uPA and integrin signaling may preserve cerebrohemodynamic control after H\/I.<\/jats:p>","DOI":"10.1152\/ajpheart.01141.2008","type":"journal-article","created":{"date-parts":[[2009,1,24]],"date-time":"2009-01-24T02:39:03Z","timestamp":1232764743000},"page":"H862-H867","source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of integrin \u03b1<sub>V<\/sub>\u03b2<sub>3<\/sub>prevents urokinase plasminogen activator-mediated impairment of cerebrovasodilation after cerebral hypoxia\/ischemia"],"prefix":"10.1152","volume":"296","author":[{"given":"J. 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