TNF-alpha antagonism with etanercept enhances penile NOS expression, cavernosal reactivity, and testosterone levels in aged rats


Demirtaş Şahin T. , Yazır Y. , Utkan T. , Gacar G. , Rencber S. H. , Göçmez S. S.

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, vol.96, pp.200-207, 2018 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 96
  • Publication Date: 2018
  • Doi Number: 10.1139/cjpp-2017-0113
  • Title of Journal : CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
  • Page Numbers: pp.200-207
  • Keywords: 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

Abstract

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.