AIMS - 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.
METHODS - 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 [(3) H]-noradrenaline efflux, western blotting for α1 and β1 sGC subunits, and cyclic nucleotide levels were carried out.
RESULTS - 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(-4) g/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 [(3) H]-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.
CONCLUSI0NS - 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. © 2016 Wiley Periodicals, Inc.
Neurourology and urodynamics. 2016 Mar 21 [Epub ahead of print]
Fabiano B Calmasini, Fabio H Silva, Eduardo C Alexandre, Renata L Rodrigues, Ana Paula L Barbosa, Danilo L Ferrucci, Hernandes F Carvalho, Gabriel F Anhê, Andre S Pupo, Edson Antunes
Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Department of Structural and Functional Biology, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil., Department of Structural and Functional Biology, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil., Department of Structural and Functional Biology, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil., Department of Pharmacology, Institute of Biosciences, University of São Paulo State (UNESP), Botucatu, São Paulo, Brazil., Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.