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The purpose of the current study was to investigate the effect of NO donors on migration of primary cultures of rat aortic smooth muscle cells and to compare and contrast their response with those in subcultured cells. A second purpose was to investigate some of the underlying mechanisms associated with NO-induced effects on cell migration. We report that 2 NO donors,<jats:italic>S<\/jats:italic>-nitroso-<jats:italic>N<\/jats:italic>-acetylpenicillamine (SNAP) and 2,2-(hydroxynitrosohydrazino)bis-ethanamine, stimulated the migration of primary cells in a wounded-culture model as well as in a transwell migration model. The effect of NO donors was mimicked by 2 cGMP analogues and C-type natriuretic peptide and blocked by a specific inhibitor of guanyl cyclase, 1H-(1,2,4)oxadiazolo[4,3,-a]quinoxalin-1-one, indicating the involvement of cGMP as second messenger. Moreover, neither NO donors nor cGMP analogues altered migration of primary cultures stimulated by either FBS or angiotensin II. In contrast to its effect in primary cultures, SNAP did not alter basal or stimulated migration of subcultured cells, except at a relatively high concentration of 1 mmol\/L, at which migration was inhibited. The migration-stimulatory effect of NO donors and cGMP was associated with altered cell morphology and dissociation of actin filaments, consistent with recent studies indicating that cell morphology and cytoskeletal organization influence cell migration. The results suggest the possible involvement of NO-induced cell migration in vascular injury or remodeling, representing conditions in which vascular NO levels would be expected to be elevated.<\/jats:p>","DOI":"10.1161\/01.res.84.6.655","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"655-667","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["Nitric Oxide and C-Type Atrial Natriuretic Peptide Stimulate Primary Aortic Smooth Muscle Cell Migration via a cGMP-Dependent Mechanism"],"prefix":"10.1161","volume":"84","author":[{"given":"Claire","family":"Brown","sequence":"first","affiliation":[{"name":"From the Department of Physiology and Biophysics, University of Tennessee, 894 Union Ave, Memphis, Tenn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Pan","sequence":"additional","affiliation":[{"name":"From the Department of Physiology and Biophysics, University of Tennessee, 894 Union Ave, Memphis, Tenn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aviv","family":"Hassid","sequence":"additional","affiliation":[{"name":"From the Department of Physiology and Biophysics, University of Tennessee, 894 Union Ave, Memphis, Tenn."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.86.3.1516183"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119472"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0033-0620(97)80031-X"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-5214(98)70296-4"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.47.1.365"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.16.10.1256"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.57.030195.003423"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.82.1.21"},{"key":"e_1_3_2_9_2","first-page":"77","volume":"75","year":"1996","unstructured":"Buttery LD, Springall DR, Chester AH, Evans TJ, Standfield EN, Parums DV, Yacoub MH, Polak JM. 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