TNF-alpha antagonism with etanercept enhances penile NOS expression, cavernosal reactivity, and testosterone levels in aged rats
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, cilt.96, ss.200-207, 2018 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 96
- Basım Tarihi: 2018
- Doi Numarası: 10.1139/cjpp-2017-0113
- Dergi Adı: CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.200-207
- Anahtar Kelimeler: erectile dysfunction, aging, etanercept, TNF-alpha, inflammation, eNOS, nNOS, NITRIC-OXIDE SYNTHASE, CARDIOVASCULAR RISK-FACTORS, MILD STRESS MODEL, ERECTILE DYSFUNCTION, ENDOTHELIAL DYSFUNCTION, VASCULAR INFLAMMATION, CORPUS CAVERNOSUM, SMOOTH-MUSCLE, GENE-TRANSFER, MEN
- Kocaeli Üniversitesi Adresli: Evet
Özet
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.