title: Oxidative stress associated with middle aging leads to sympathetic hyperactivity and downregulation of soluble guanylyl cyclase in corpus cavernosum.
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 α₁/β₁-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 α₁/β₁-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 α₁/β₁-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.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences and Department of Anatomy, Cellular Biology, Physiology and Biophysics, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil; and.
authors.forename: Fábio H
authors.initials: FH
authors.lastname: Silva
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences and Department of Anatomy, Cellular Biology, Physiology and Biophysics, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil; and.
authors.forename: Carolina
authors.initials: C
authors.lastname: Lanaro
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences and Department of Anatomy, Cellular Biology, Physiology and Biophysics, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil; and.
authors.forename: Luiz Osório
authors.initials: LO
authors.lastname: Leiria
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences and Department of Anatomy, Cellular Biology, Physiology and Biophysics, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil; and.
authors.forename: Renata Lopes
authors.initials: RL
authors.lastname: Rodrigues
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences and Department of Anatomy, Cellular Biology, Physiology and Biophysics, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil; and.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Davel
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences and Department of Anatomy, Cellular Biology, Physiology and Biophysics, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil; and.
authors.forename: Mário A
authors.initials: MA
authors.lastname: Claudino
authors.affiliation: Department of Pharmacology and Toxicology, Georgia Health Sciences University, Augusta, Georgia.
authors.forename: Haroldo A
authors.initials: HA
authors.lastname: Toque
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences and Department of Anatomy, Cellular Biology, Physiology and Biophysics, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil; and edson.antunes@uol.com.br.
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D018783:Impotence, Vasculogenic / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000201:enzymology / Q000294:innervation*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000098:blood supply / Q000294:innervation*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase; D013481:Superoxides; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: C547715:Adra1a protein, rat; D058646:Adrenergic alpha-1 Receptor Agonists; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D018160:Receptors, Cytoplasmic and Nuclear; D013481:Superoxides; D014446:Tyrosine 3-Monooxygenase; D019255:NADPH Oxidases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase
keywords: NADPH oxidase; antioxidant therapy; apocynin; reactive-oxygen species; superoxide anion; tyrosine hydroxylase