{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:03:28Z","timestamp":1787792608098,"version":"build-2784847793"},"reference-count":48,"publisher":"Canadian Science Publishing","issue":"2","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p> Erectile dysfunction (ED) has been reported to be associated with inflammation. This study investigated the effects of tumor necrosis factor alpha (TNF-\u03b1) inhibitor etanercept on penile neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) expressions, testosterone concentrations, neurogenic and endothelium-dependent relaxations of corpus cavernosum (CC), and circulating and cavernosal levels of inflammatory markers in aged rats. Animals were separated into control, aged, and etanercept-treated aged groups. Aged rats displayed significantly increased serum and cavernosal TNF-\u03b1, C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule (ICAM\u20131) levels, and decreased penile nNOS and eNOS expressions and serum testosterone levels compared with controls. In etanercept-treated aged group, NOS expressions were similar to that of the control group. The circulating and cavernosal concentrations of TNF-\u03b1, CRP, MCP-1, ICAM-1, and testosterone were also normalized by etanercept. Neurogenic and endothelium-dependent relaxant responses significantly decreased in aged rats and etanercept treatment markedly improved these relaxation responses. Our findings indicate that aging decreases penile NOS expression, neurogenic and endothelium-dependent relaxations of CC, and also suppresses serum testosterone levels by inducing inflammatory response that may contribute to the development of ED. TNF-\u03b1 antagonism may be a novel strategy to treat aging-associated ED. <\/jats:p>","DOI":"10.1139\/cjpp-2017-0113","type":"journal-article","created":{"date-parts":[[2017,12,20]],"date-time":"2017-12-20T14:19:06Z","timestamp":1513779546000},"page":"200-207","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["TNF-\u03b1 antagonism with etanercept enhances penile NOS expression, cavernosal reactivity, and testosterone levels in aged rats"],"prefix":"10.1139","volume":"96","author":[{"given":"Tu\u011f\u00e7e","family":"Demirta\u015f \u015eahin","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Medical Faculty, Kocaeli University, Kocaeli 41380, Turkey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusufhan","family":"Yazir","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Kocaeli University, Kocaeli 41380, Turkey."},{"name":"Stem Cell and Gene Therapy Research and Application Center, Kocaeli University, Kocaeli 41380, Turkey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tijen","family":"Utkan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical Faculty, Kocaeli University, Kocaeli 41380, Turkey."},{"name":"Experimental Medical Research and Application Center, Kocaeli University, Kocaeli 41380, Turkey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulcin","family":"Gacar","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Research and Application Center, Kocaeli University, Kocaeli 41380, Turkey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selenay","family":"Furat Ren\u00e7ber","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Kocaeli University, Kocaeli 41380, Turkey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semil Selcen","family":"Gocmez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical Faculty, Kocaeli University, Kocaeli 41380, Turkey."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.2009.02426.x"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.04.007"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.2006.00730.x"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijir.3901012"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijir.3900556"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00770.2002"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061466"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000116325.06572.85"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)65369-2"},{"issue":"3","key":"refg10\/ref10","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/BF03401627","volume":"2","author":"Burnett A.L.","year":"1996","journal-title":"Mol. 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