{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:43:03Z","timestamp":1791272583475,"version":"4.1.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:p>Intermittent hypoxia (IH) resulting from sleep apnea causes both systemic and pulmonary hypertension. Enhanced endothelin-1 (ET-1)-induced vasoconstrictor reactivity is thought to play a central role in the systemic hypertensive response to IH. However, whether IH similarly increases pulmonary vasoreactivity and the signaling mechanisms involved are unknown. The objective of the present study was to test the hypothesis that IH augments ET-1-induced pulmonary vasoconstrictor reactivity through a PKC\u03b2-dependent signaling pathway. Responses to ET-1 were assessed in endothelium-disrupted, pressurized pulmonary arteries (\u223c150 \u03bcm inner diameter) from eucapnic-IH [(E-IH) 3 min cycles, 5% O<jats:sub>2<\/jats:sub>-5% CO<jats:sub>2<\/jats:sub>\/air flush, 7 h\/day; 4 wk] and sham (air-cycled) rats. Arteries were loaded with fura-2 AM to monitor vascular smooth muscle (VSM) intracellular Ca<jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>). E-IH increased vasoconstrictor reactivity without altering Ca<jats:sup>2+<\/jats:sup>responses, suggestive of myofilament Ca<jats:sup>2+<\/jats:sup>sensitization. Consistent with our hypothesis, inhibitors of both PKC\u03b1\/\u03b2 (myr-PKC) and PKC\u03b2 (LY-333-531) selectively decreased vasoconstriction to ET-1 in arteries from E-IH rats and normalized responses between groups, whereas Rho kinase (fasudil) and PKC\u03b4 (rottlerin) inhibition were without effect. Although E-IH did not alter arterial PKC\u03b1\/\u03b2 mRNA or protein expression, E-IH increased basal PKC\u03b2I\/II membrane localization and caused ET-1-induced translocation of these isoforms away from the membrane fraction. We conclude that E-IH augments pulmonary vasoconstrictor reactivity to ET-1 through a novel PKC\u03b2-dependent mechanism that is independent of altered PKC expression. These findings provide new insights into signaling mechanisms that contribute to vasoconstriction in the hypertensive pulmonary circulation.<\/jats:p>","DOI":"10.1152\/ajplung.00020.2011","type":"journal-article","created":{"date-parts":[[2011,7,30]],"date-time":"2011-07-30T03:00:29Z","timestamp":1311994829000},"page":"L745-L754","source":"Crossref","is-referenced-by-count":26,"title":["Role for PKC\u03b2 in enhanced endothelin-1-induced pulmonary vasoconstrictor reactivity following intermittent hypoxia"],"prefix":"10.1152","volume":"301","author":[{"given":"Jessica B.","family":"Snow","sequence":"first","affiliation":[{"name":"Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura V.","family":"Gonzalez Bosc","sequence":"additional","affiliation":[{"name":"Vascular Physiology Group, Department of Cell Biology and Physiology, 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