{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:17:11Z","timestamp":1790421431193,"version":"4.1.0"},"reference-count":57,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2002,1,1]]},"abstract":"<jats:p>\n                    Nitric oxide (NO) is an endogenous endothelium-derived relaxing factor that regulates vascular smooth muscle cell proliferation and apoptosis. This study investigated underlying mechanisms involved in NO-induced apoptosis in human and rat pulmonary artery smooth muscle cells (PASMC). Exposure of PASMC to NO, which was derived from the NO donor S-nitroso- N-acetyl-penicillamine, increased the percentage of cells undergoing apoptosis. Increasing extracellular K\n                    <jats:sup>+<\/jats:sup>\n                    concentration to 40 mM or blocking K\n                    <jats:sup>+<\/jats:sup>\n                    channels with 1 mM tetraethylammonia (TEA), 100 nM iberiotoxin (IBTX), and 5 mM 4-aminopyridine (4-AP) significantly inhibited the NO-induced apoptosis. In single PASMC, NO reversibly increased K\n                    <jats:sup>+<\/jats:sup>\n                    currents through the large-conductance Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated K\n                    <jats:sup>+<\/jats:sup>\n                    (K\n                    <jats:sub>Ca<\/jats:sub>\n                    ) channels, whereas TEA and IBTX markedly decreased the K\n                    <jats:sub>Ca<\/jats:sub>\n                    currents. In the presence of TEA, NO also increased K\n                    <jats:sup>+<\/jats:sup>\n                    currents through voltage-gated K\n                    <jats:sup>+<\/jats:sup>\n                    (K\n                    <jats:sub>v<\/jats:sub>\n                    ) channels, whereas 4-AP significantly decreased the K\n                    <jats:sub>v<\/jats:sub>\n                    currents. Opening of K\n                    <jats:sub>Ca<\/jats:sub>\n                    channels with 0.3 mM dehydroepiandrosterone increased K\n                    <jats:sub>Ca<\/jats:sub>\n                    currents, induced apoptosis, and further enhanced the NO-mediated apoptosis. Furthermore, NO depolarized the mitochondrial membrane potential. These observations indicate that NO induces PASMC apoptosis by activating K\n                    <jats:sub>Ca<\/jats:sub>\n                    and K\n                    <jats:sub>v<\/jats:sub>\n                    channels in the plasma membrane. The resulting increase in K\n                    <jats:sup>+<\/jats:sup>\n                    efflux leads to cytosolic K\n                    <jats:sup>+<\/jats:sup>\n                    loss and eventual apoptosis volume decrease and apoptosis. NO-induced apoptosis may also be related to mitochondrial membrane depolarization in PASMC.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.2002.282.1.h184","type":"journal-article","created":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T15:28:10Z","timestamp":1513956490000},"page":"H184-H193","source":"Crossref","is-referenced-by-count":61,"title":["Nitric oxide induces apoptosis by activating K\n                    <sup>+<\/sup>\n                    channels in pulmonary vascular smooth muscle cells"],"prefix":"10.1152","volume":"282","author":[{"given":"Stefanie","family":"Krick","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California School of Medicine, San Diego, California 92103-8382"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandr","family":"Platoshyn","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, 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