PMID- 29260891 OWN - NLM STAT- MEDLINE DCOM- 20180810 LR - 20180810 IS - 1205-7541 (Electronic) IS - 0008-4212 (Linking) VI - 96 IP - 2 DP - 2018 Feb TI - TNF-alpha antagonism with etanercept enhances penile NOS expression, cavernosal reactivity, and testosterone levels in aged rats. PG - 200-207 LID - 10.1139/cjpp-2017-0113 [doi] AB - Erectile dysfunction (ED) has been reported to be associated with inflammation. This study investigated the effects of tumor necrosis factor alpha (TNF-alpha) 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-alpha, C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule (ICAM-1) 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-alpha, 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-alpha antagonism may be a novel strategy to treat aging-associated ED. FAU - Demirtas Sahin, Tugce AU - Demirtas Sahin T AD - a Department of Pharmacology, Medical Faculty, Kocaeli University, Kocaeli 41380, Turkey. FAU - Yazir, Yusufhan AU - Yazir Y AD - b Department of Histology and Embryology, Medical Faculty, Kocaeli University, Kocaeli 41380, Turkey. AD - c Stem Cell and Gene Therapy Research and Application Center, Kocaeli University, Kocaeli 41380, Turkey. FAU - Utkan, Tijen AU - Utkan T AD - a Department of Pharmacology, Medical Faculty, Kocaeli University, Kocaeli 41380, Turkey. AD - d Experimental Medical Research and Application Center, Kocaeli University, Kocaeli 41380, Turkey. FAU - Gacar, Gulcin AU - Gacar G AD - c Stem Cell and Gene Therapy Research and Application Center, Kocaeli University, Kocaeli 41380, Turkey. FAU - Furat Rencber, Selenay AU - Furat Rencber S AD - b Department of Histology and Embryology, Medical Faculty, Kocaeli University, Kocaeli 41380, Turkey. FAU - Gocmez, Semil Selcen AU - Gocmez SS AD - a Department of Pharmacology, Medical Faculty, Kocaeli University, Kocaeli 41380, Turkey. LA - eng PT - Journal Article DEP - 20171220 PL - Canada TA - Can J Physiol Pharmacol JT - Canadian journal of physiology and pharmacology JID - 0372712 RN - 0 (Biomarkers) RN - 0 (Tumor Necrosis Factor-alpha) RN - 3XMK78S47O (Testosterone) RN - 8Y164V895Y (Carbachol) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type I) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - OP401G7OJC (Etanercept) SB - IM MH - Aging/*blood MH - Animals MH - Biomarkers/blood MH - Body Weight/drug effects MH - Carbachol/pharmacology MH - Electric Stimulation MH - Endothelium, Vascular/drug effects/metabolism MH - Etanercept/*pharmacology MH - Inflammation/blood/pathology MH - Male MH - Nitric Oxide Synthase Type I/*metabolism MH - Nitric Oxide Synthase Type III/*metabolism MH - Organ Size/drug effects MH - Penis/*enzymology MH - Rats, Wistar MH - Testosterone/*blood MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/metabolism MH - Vasodilation/drug effects OTO - NOTNLM OT - TNF-alpha OT - aging OT - dysfonction erectile OT - eNOS OT - erectile dysfunction OT - etanercept OT - inflammation OT - nNOS OT - vieillissement OT - etanercept EDAT- 2017/12/21 06:00 MHDA- 2018/08/11 06:00 CRDT- 2017/12/21 06:00 PHST- 2017/12/21 06:00 [pubmed] PHST- 2018/08/11 06:00 [medline] PHST- 2017/12/21 06:00 [entrez] AID - 10.1139/cjpp-2017-0113 [doi] PST - ppublish SO - Can J Physiol Pharmacol. 2018 Feb;96(2):200-207. doi: 10.1139/cjpp-2017-0113. Epub 2017 Dec 20.