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We demonstrated that in SMCs from old rats, NO was unable to increase the concentration of intracellular cGMP, suggesting that either cGMP synthesis was defective or cGMP degradation was enhanced. Western blot analysis revealed that SMCs from old rats do not express the \u03b2 subunit of soluble guanylyl cyclase. To confirm the importance of this observation in vivo, we balloon-injured the carotid arteries of adult and old rats. Whereas soluble guanylyl cyclase was expressed at the same level in the media of injured vessels and uninjured vessels of both groups, its expression in the intimas of old rats was reduced by 70% compared with intimas from adult animals. Furthermore,<jats:italic>N<\/jats:italic><jats:sup>\u03c9<\/jats:sup>-nitro-<jats:sc>l<\/jats:sc>-arginine, an inhibitor of NO synthesis, enhanced the intimal thickening in injured vessels in adult rats but not in old rats. We conclude that the loss of NO responsiveness in aged rats is due to the lack of the \u03b2 subunit of soluble guanylyl cyclase, and we speculate that this defect contributes to the enhanced intimal thickening in response to injury in old animals.<\/jats:p>","DOI":"10.1161\/01.res.86.5.520","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:52:16Z","timestamp":1339462336000},"page":"520-525","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Loss of Expression of the \u03b2 Subunit of Soluble Guanylyl Cyclase Prevents Nitric Oxide\u2013Mediated Inhibition of DNA Synthesis in Smooth Muscle Cells of Old Rats"],"prefix":"10.1161","volume":"86","author":[{"given":"Lihua","family":"Chen","sequence":"first","affiliation":[{"name":"From the Departments of Surgery (L.C., G.D., J.W.F., S.H., A.W.C.), University of Washington, Seattle, and the Department of Pathology (M.-L.B.-P., G.G.), University of Geneva, CMU, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gu\u0308nter","family":"Daum","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery (L.C., G.D., J.W.F., S.H., A.W.C.), University of Washington, Seattle, and the Department of Pathology (M.-L.B.-P., G.G.), University of Geneva, CMU, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens W.","family":"Fischer","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery (L.C., G.D., J.W.F., S.H., A.W.C.), University of Washington, Seattle, and the Department of Pathology (M.-L.B.-P., G.G.), University of Geneva, CMU, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Hawkins","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery (L.C., G.D., J.W.F., S.H., A.W.C.), University of Washington, Seattle, and the Department of Pathology (M.-L.B.-P., G.G.), University of Geneva, CMU, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Luce","family":"Bochaton-Piallat","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery (L.C., G.D., J.W.F., S.H., A.W.C.), University of Washington, Seattle, and the Department of Pathology (M.-L.B.-P., G.G.), University of Geneva, CMU, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Gabbiani","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery (L.C., G.D., J.W.F., S.H., A.W.C.), University of Washington, Seattle, and the Department of Pathology (M.-L.B.-P., G.G.), University of Geneva, CMU, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander W.","family":"Clowes","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery (L.C., G.D., J.W.F., S.H., A.W.C.), University of Washington, Seattle, and the Department of Pathology (M.-L.B.-P., G.G.), University of Geneva, CMU, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/333664a0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0031-6997(25)06663-3","volume":"43","year":"1991","unstructured":"Moncada S, Palmer RMJ, Higgs EA. 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