{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:09:03Z","timestamp":1789747743774,"version":"4.0.1"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,2,16]]},"abstract":"<jats:p>\n                    Two enzymes, soluble guanylyl cyclase and cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    oxidase, have been shown to be exquisitely sensitive to nitric\n oxide (NO) at low physiological concentrations. Activation of the\n soluble guanylyl cyclase by endogenous NO and the\n consequent increase in the second messenger cyclic GMP are now known to\n control a variety of biological functions. Cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    oxidase, the terminal enzyme of the mitochondrial respiratory chain, is\n inhibited by NO. However, it is not clear whether NO produced by the\n constitutive NO synthase interacts with cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    oxidase, nor is it known what the biological consequences of such an\n interaction might be. We now show that NO generated by vascular\n endothelial cells under basal and stimulated conditions modulates the\n respiration of these cells in response to acute changes in oxygen\n concentration. This action occurs at the cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    oxidase and depends on influx of calcium. Thus, NO plays a\n physiological role in adjusting the capacity of this enzyme to use\n oxygen, allowing endothelial cells to adapt to acute changes in their\n environment.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.4.1559","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"1559-1562","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":249,"title":["On the mechanism by which vascular endothelial cells regulate their oxygen consumption"],"prefix":"10.1073","volume":"96","author":[{"given":"Emilio","family":"Clementi","sequence":"first","affiliation":[{"name":"Wolfson Institute for Biomedical Research, University College\r London, Tottenham Court Road, London W1P 9LN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy Charles","family":"Brown","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, University College\r London, Tottenham Court Road, London W1P 9LN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neale","family":"Foxwell","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, University College\r London, Tottenham Court Road, London W1P 9LN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Moncada","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, University College\r London, Tottenham Court Road, London W1P 9LN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,2,16]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68062227.x"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.75.6.1086"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.92.12.3505"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.79.3.381"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.274.1.C112"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)01290-3"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)00424-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2441"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00763-Y"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.13.7631"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1986.tb14586.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)45858-9"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1986.250.5.C663"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/327524a0"},{"key":"e_1_3_3_15_2","first-page":"319","volume-title":"Methods in Nitric Oxide Research","author":"Malinski T","year":"1996","unstructured":"T Malinski, L Czuchajowski Methods in Nitric Oxide Research, eds M Feelisch, J S Stamler (Wiley, New York), pp. 319\u2013339 (1996)."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.269.3.C757"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.10.5647"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3300695"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb12735.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.267.2.C313"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(95)00117-4"},{"key":"e_1_3_3_22_2","first-page":"L469","volume":"266","author":"Cornfield D N","year":"1994","unstructured":"D N Cornfield, T Stevens, I F McMurtry, S H Abman, D M Rodman Am J Physiol 266, L469\u2013L475 (1994).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_23_2","unstructured":"Boveris A. 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