Urethral Smooth Muscle Dysfunction in Middle‐aged Male Rats May Affect Micturition

Abstract

INTRODUCTION AND OBJECTIVESEpidemiological studies have shown that age is the most important unmodifiable risk factor of lower urinary tract symptoms (LUTS) in men. Much attention has been given to the involvement of the bladder and prostate in men's lower urinary system, however much less to the urethra. We raised the hypothesis that middle‐aged urethra smooth muscle (USM) impairment may exert a negative influence on lower urinary tract functioning. Here we aimed to evaluate the urethral main contractile and relaxant pathways through functional, biochemical, and molecular studies and their consequences to micturition.METHODSYoung (3.5‐month) and middle‐aged (10‐month) male Wistar rats were used (CEUA 4404‐1). USM was collected for functional, biochemical, and molecular assays. Urethral contractions were evaluated by electrical field stimulation (EFS) and phenylephrine (PE) and relaxations by sodium nitroprusside (SNP) and glyceryl trinitrate (GTN). cGMP was measured and qRT‐PCR was conducted for different gene targets like NOS enzymes, sGCβ1, PDE5, MRP5, gp91phox, HIF1α, SOD1, and catalase. Anion superoxide, NO, collagen, and smooth‐muscle area were also measured and a cystometric analysis was performed.RESULTSContractile responses elicited by EFS (1–16 Hz) and PE were greater in USM for the middle‐aged group compared with the young group, an alteration that was accompanied by a decrease in NO‐induced USM relaxation by SNP and GTN. cGMP concentration was lower in the middle‐aged USM compared with the young group. In qRT‐PCR, up‐regulation of PDE5, MRP5, gp91phox, and HIF1α, associated with down‐regulation of sGCβ1, SOD1, and catalase were observed in middle‐aged USM. No differences of NOS enzymes expression were found. The anion superoxide and NO levels in the USM of middle‐aged rats were increased and decreased, respectively. This was accompanied by higher USM collagen and smooth muscle area. Middle‐aged rats showed an irregular micturition pattern characterized by significant increases of basal pressure, capacity, and compliance.CONCLUSIONSUSM dysfunction in middle‐aged rats due to the association with NO‐cGMP pathway impairment and oxidative stress may represent a detrimental factor to micturition and the start of bladder alterations observed in the elderly.Support or Funding InformationSource of funding: FAPESP (2017/04556‐4 and 2018/03625‐5)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.