{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:16:34Z","timestamp":1777529794487,"version":"3.51.4"},"reference-count":33,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[1998,6,1]],"date-time":"1998-06-01T00:00:00Z","timestamp":896659200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cardiovasc Pharmacol Ther"],"published-print":{"date-parts":[[1998,6]]},"abstract":"<jats:p>Background: Nitric oxide (NO), a potent vasodilator and inhibitor of platelet function, is elaborated constitutively by endothelial cells through the oxidation of L-arginine by endo thelial NO synthase. Although several biochemical agonists, such as bradykinin, have been shown to stimulate NO production by the endothelium, the effects of physical factors have been less well characterized. We have previously examined the shear-stress-dependent induction of NO production by the endothelium, and others have examined the effects of transmural pressure on NO production. In the current study, we analyzed the effects of cyclic strain or load in the presence and absence of an NO agonist on endothelial cell proliferation.<\/jats:p>\n                  <jats:p>\n                    Methods and Results: Subconfluent human microvascular endothelial cells were grown on deformable culture plates in media containing 10% fetal bovine serum and 1 mM L-arginine, and then subjected to either 0, 11, 18, or 27% cyclic strain at a frequency of 1 Hz. Nitrogen oxides (S-nitrosothiols and free NO) in media were measured by photolysis-chemilumines cence at the end of 24 hours, as were cell number, [\n                    <jats:sup>3<\/jats:sup>\n                    H]thymidine incorporation, and total cell protein. In the absence of an NO agonist, 11 % cyclic strain produced a 73 \u00b1 17% increase in nitrogen oxides compared with control ( P &lt; .05), whereas 18 and 27% cyclic strain produced no significant increase in nitrogen oxides compared with control. However, cells subjected to 27% strain increased cell number (by 98 \u00b1 17%) and [\n                    <jats:sup>3<\/jats:sup>\n                    H]thymidine incor poration (by 16 \u00b1 4%, P &lt; .05) compared with control. In an attempt to examine further the effects of endogenous NO on the cells' proliferative response to increasing levels of cyclic strain, we incubated human microvascular endothelial cells with 1 \u03bcM bradykinin and subjected them to 27% cyclic strain. In the presence of bradykinin and 27% cyclic strain, production of nitrogen oxides and endothelial NO synthase activity were increased by 110 \u00b1 37% and 135 \u00b1 7%, respectively ( P &lt; .05 compared with control); however, we observed no significant increase in cell number (5 \u00b1 5%), despite an 86 \u00b1 7% increase in [\n                    <jats:sup>3<\/jats:sup>\n                    H]thymi- dine incorporation (P &lt; .05).\n                  <\/jats:p>\n                  <jats:p>Conclusions: These results suggest that endogenous NO production by human microvascu lar endothelial cells regulates their growth response to cyclic strain. Modulation of NO pro duction in vivo in areas of the vasculature that are subjected to increased levels of strain may represent one potential mechanism by which to alter endothelial cell proliferation.<\/jats:p>","DOI":"10.1177\/107424849800300206","type":"journal-article","created":{"date-parts":[[2007,11,26]],"date-time":"2007-11-26T17:52:29Z","timestamp":1196099549000},"page":"135-141","source":"Crossref","is-referenced-by-count":10,"title":["Nitric Oxide Alters Human Microvascular Endothelial Cell Response to Cyclic Strain"],"prefix":"10.1177","volume":"3","author":[{"suffix":"JR","given":"Gilbert R.","family":"Upchurch","sequence":"first","affiliation":[{"name":"Whitaker Cardiovascular Instittete and Evans Department of Medicine, Boston University School of Medicine, Department of Surgery, Brigham and Women 's Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane A.","family":"Leopold","sequence":"additional","affiliation":[{"name":"Whitaker Cardiovascular Instittete and Evans Department of Medicine, Boston University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George N.","family":"Welch","sequence":"additional","affiliation":[{"name":"Whitaker Cardiovascular Instittete and Evans Department of Medicine, Boston University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Loscalzo","sequence":"additional","affiliation":[{"name":"Whitaker Cardiovascular Instittete and Evans Department of Medicine, Boston University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[1998,6,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1038\/288373a0"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.24.9265"},{"key":"atypb3","doi-asserted-by":"publisher","DOI":"10.1038\/345161a0"},{"key":"atypb4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.16.7674"},{"key":"atypb5","first-page":"804","volume":"28","author":"Cooke JP","year":"1990","journal-title":"Am J Physiol"},{"key":"atypb6","doi-asserted-by":"crossref","first-page":"H1145","DOI":"10.1152\/ajpcell.1986.250.3.C406","volume":"250","author":"Rubanyi GM","year":"1986","journal-title":"Am J Physiol"},{"key":"atypb7","first-page":"109","volume":"18","author":"Kaiser L.","year":"1986","journal-title":"Circ Shock"},{"key":"atypb8","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)90051-5"},{"key":"atypb9","doi-asserted-by":"publisher","DOI":"10.1016\/0741-5214(87)90037-1"},{"key":"atypb10","first-page":"A911","volume":"4","author":"Upchurch GR Jr","year":"1990","journal-title":"FASEB J"},{"key":"atypb11","doi-asserted-by":"publisher","DOI":"10.1016\/0741-5214(88)90386-2"},{"key":"atypb12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107470"},{"key":"atypb13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107471"},{"key":"atypb14","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(96)68031-8"},{"key":"atypb15","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1242\/jcs.75.1.35","volume":"75","author":"Banes AJ","year":"1985","journal-title":"J Cell Sci"},{"key":"atypb16","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041230304"},{"key":"atypb17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.2.682"},{"key":"atypb18","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4804(88)90103-5"},{"key":"atypb19","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1988.01400340059010"},{"key":"atypb20","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9290(94)90057-4"},{"key":"atypb21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.10.4591"},{"key":"atypb22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.14.6348"},{"key":"atypb23","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4781(94)90195-3"},{"key":"atypb24","doi-asserted-by":"publisher","DOI":"10.3109\/10623329409088469"},{"key":"atypb25","first-page":"459","volume":"112","author":"Rosales OR","year":"1992","journal-title":"Surgery"},{"key":"atypb26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1992.262.4.C956"},{"key":"atypb27","first-page":"634","volume":"31","author":"Letsou GV","year":"1990","journal-title":"J Cardiovasc Surg"},{"key":"atypb28","doi-asserted-by":"publisher","DOI":"10.1126\/science.2173861"},{"key":"atypb29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118181"},{"key":"atypb30","first-page":"439","volume":"116","author":"Awolesi MA","year":"1994","journal-title":"Surgery"},{"key":"atypb31","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2304"},{"key":"atypb32","doi-asserted-by":"crossref","unstructured":"Bogle RG, Coade SB, Moncada S., Pearson JD, Mann GE Bradykinin stimulates L-arginine transport and nitric oxide release in vascular endothelial cells. In Moncada S, Marletta MA, Hibbs JB Jr, Higgs EA (eds). The Biology of Nitric Oxide. Physiological and Clinical Aspects. Port-land Press: London, pp. 65-68, 1992","DOI":"10.1007\/978-1-4615-2437-3_16"},{"key":"atypb33","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.74.6.1220"}],"container-title":["Journal of Cardiovascular Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/107424849800300206","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/107424849800300206","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:40:34Z","timestamp":1777394434000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/107424849800300206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,6]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1998,6]]}},"alternative-id":["10.1177\/107424849800300206"],"URL":"https:\/\/doi.org\/10.1177\/107424849800300206","relation":{},"ISSN":["1074-2484","1940-4034"],"issn-type":[{"value":"1074-2484","type":"print"},{"value":"1940-4034","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,6]]}}}