20,21 These hypotheses are partly duplicated and poorly understood in the elucidation of the BPH/LUTS–ED relationship; therefore, the exact mechanisms should be further investigated.22 NO-cGMP signal pathway has been considered to have an invaluable functional role in the human prostate. NO also has been identified as the important signaling molecule for penile erection. In recent years, it has been recognized that reducing NO production and usefulness is linked to the development of BPH/LUTS. As a consequence, there is increasing interest in the NO-cGMP signaling

pathway as a potential pharmacological target to treat BPH/LUTS. NOS is found in the normal prostate in two isoforms: eNOS and nNOS, not only in HIF inhibitor nerve fibers transversing the fibromuscular prostatic stroma, but also in the cytoplasm of basal cells.12,23 NOS expression resulting in NO production is reduced in the transition zone of the prostate in BPH, compared with normal prostate tissue.24 The proposed reduction in expression of NOS isoforms resulted in increased smooth muscle cell contraction at the bladder neck and prostatic urethra leading to bladder

outlet obstruction (BOO). Additionally, NO bioavailability results in prostatic smooth muscle cell proliferation, which further contributes to increasing

BOO. PDE5 expression in the striated muscle of the urethra and levator ani in rats has been identified.25 C646 chemical structure The detection of PDE5 expression in striated muscle of the urethra and levator ani could lead to a better comprehension of urethral and pelvic floor disharmony, which can cause LUTS. The integrity of the autonomic nervous system (ANS) and its releasing neurotransmitters is essential for erectile function and lower urinary tract function. A significant association between ANS activity and both disorders is evident in recent research data. Autonomic hyperactivity involves discord of parasympathetic and sympathetic tone, and increased sympathetic tone causes increment of smooth Methocarbamol muscle tone in the bladder outlet and prostate.26 Rat models demonstrated an effect on prostatic growth and differentiation through handling of autonomic activity.27 In aging rats, the development of BPH/LUTS and ED was enhanced by increased ANS activity.28 A recent epidemiological study of the relationship between MS and LUTS hypothesized that MS is associated with bladder overactivity and increased urinary frequency, and that hyperinsulinemia might be an essential element of MS.