title: Implication of Rho-kinase and soluble guanylyl cyclase enzymes in prostate smooth muscle dysfunction in middle-aged rats.
abstract: Aging is highly associated with benign prostate hyperplasia (BPH). We investigated here the alterations of the contractile and relaxant machinery in prostates of middle-aged rats, focusing on the Rho-kinase, nitric oxide (NO)-soluble guanylyl cyclase (sGC), α1- and β-adrenoceptor pathways.
  
  
  
  Male Wistar young (3.5-month old) and middle-aged rats (10-month old) were used. Quantitative image analysis of prostates and functional assays evaluating the prostate contractions and relaxations were employed. Measurement of [3H]-noradrenaline efflux, western blotting for α1 and β1 sGC subunits, and cyclic nucleotide levels were carried out.
  
  
  
  Prostates of middle-aged rats showed significant increases in lumen and smooth muscle cells, but no alterations in the relative prostate weight were observed. In vivo, noradrenaline (10-7-10-4g/kg) produced greater prostatic contractions in middle-aged compared with control rats. Likewise, the in vitro contractions to phenylephrine (1 nM-100 μM) and α,β-methylene ATP (1-10 μM) were greater in middle-aged rats. Electrical-field stimulation (EFS, 1-32 Hz) promoted higher [3H]-noradrenaline efflux and prostate contractions in middle-aged rats. Reduced expressions of α1 and β1 sGC subunits and diminished NO-mediated prostate relaxations in middle-age were observed. Isoproterenol-induced relaxations and cAMP levels were reduced in prostates of middle-aged rats. The Rho-kinase inhibitor fasudil (50 mg/kg, 2 weeks) normalized the prostate hypercontractility in middle-age rats.
  
  
  
  Prostate hypercontractility in middle-aging is associated with increased release of noradrenaline and Rho-kinase pathway, as well as with impairments of NO-sGC and β-adrenoceptor pathways. Middle-aged rats are suitable to explore the enhanced prostatic tone in the absence of prostate overgrowth. Neurourol. Urodynam. 36:589-596, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Fabiano B
authors.initials: FB
authors.lastname: Calmasini
authors.affiliation: Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Fabio H
authors.initials: FH
authors.lastname: Silva
authors.affiliation: Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Eduardo C
authors.initials: EC
authors.lastname: Alexandre
authors.affiliation: Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Renata L
authors.initials: RL
authors.lastname: Rodrigues
authors.affiliation: Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Ana Paula L
authors.initials: AP
authors.lastname: Barbosa
authors.affiliation: Department of Structural and Functional Biology, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Danilo L
authors.initials: DL
authors.lastname: Ferrucci
authors.affiliation: Department of Structural and Functional Biology, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Hernandes F
authors.initials: HF
authors.lastname: Carvalho
authors.affiliation: Department of Structural and Functional Biology, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Gabriel F
authors.initials: GF
authors.lastname: Anhê
authors.affiliation: Department of Pharmacology, Institute of Biosciences, University of São Paulo State (UNESP), Botucatu, São Paulo, Brazil.
authors.forename: Andre S
authors.initials: AS
authors.lastname: Pupo
authors.affiliation: Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism* / Q000503:physiopathology; D009638:Norepinephrine / Q000378:metabolism; D011467:Prostate / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D000071756:Soluble Guanylyl Cyclase / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D054460:rho-Associated Kinases; D000071756:Soluble Guanylyl Cyclase; D009638:Norepinephrine
keywords: aging; cyclic AMP; protein kinase C; stereology; β-adrenoceptors