Oxidative stress associated with middle aging leads to sympathetic hyperactivity and downregulation of soluble guanylyl cyclase in corpus cavernosum

Fábio H. Silva, Carolina Lanaro, Luiz Osório Leiria, Renata Lopes Rodrigues, Ana Paula Davel, Mário A. Claudino, Haroldo A. Toque, Edson Antunes

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Impairment of nitric oxide (NO)-mediated cavernosal relaxations in middle age contributes to erectile dysfunction. However, little information is available about the alterations of sympathetic neurotransmission and contraction in erectile tissue at middle age. This study aimed to evaluate the alterations of the contractile machinery associated with tyrosine hydroxylase (TH) in rat corpus cavernosum (RCC) at middle age, focusing on the role of superoxide anion. Male Wistar young (3.5-mo) and middle-aged (10-mo) rats were used. Electrical-field stimulation (EFS)- and phenylephrine-induced contractions were obtained in RCC strips. Levels of reactive-oxygen species (ROS) and TH mRNA expression, as well as protein expressions for α11-subunits of soluble guanylyl cyclase (sGC), in RCC were evaluated. The neurogenic contractile responses elicited by EFS (4–32 Hz) were greater in RCC from the middle-aged group that was accompanied by elevated TH mRNA expression (P < 0.01). Phenylephrine-induced contractions were also greater in the middle-aged group. A 62% increase in ROS generation in RCC from middle-aged rats was observed. The mRNA expression for the α1A-adrenoceptor remained unchanged among groups. Protein levels of α11-sGC subunits were decreased in RCC from the middle-aged compared with young group. The NADPH oxidase inhibitor apocynin (85 mg•rat−1•day−1, 4 wk) fully restored the enhanced ROS production, TH mRNA expressions, and α11-subunit sGC expression, indicating that excess of superoxide anion plays a major role in the sympathetic hyperactivity and hypercontractility in erectile tissue at middle age. Reduction of oxidative stress by dietary antioxidants may be an interesting approach to treat erectile dysfunction in aging population.

Original languageEnglish (US)
Pages (from-to)H1393-H1400
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume307
Issue number10
DOIs
StatePublished - Nov 15 2014

Keywords

  • Antioxidant therapy
  • Apocynin
  • NADPH oxidase
  • Reactive-oxygen species
  • Superoxide anion
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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