Implication of Rho‐kinase and soluble guanylyl cyclase enzymes in prostate smooth muscle dysfunction in middle‐aged rats

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 [3H]‐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 [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. Conclusions 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.