31,32 MS is also a risk factor for the development of ED. Autonomic hyperactivity and a component of MS refer to a dysregulation of sympathetic and parasympathetic Vismodegib molecular weight tones. Increased sympathetic tone results in penile flaccidity and worsens relaxation penile cavernosum smooth muscle and prostate smooth muscle. MS may play a key role in the pathogenesis in both ED and LUTS. An abnormally upregulated Rho kinase/Rho A protein pathway contributes abnormal alteration of smooth muscle tone in the prostate, urethra, bladder neck, and penis, resulting in changes in bladder compliance leading to LUTS and ED.26 Contraction of smooth muscle

is stimulated by the inhibition of myosin light chain phosphatase by Rho kinase, which provides a calcium-independent mechanism for smooth muscle contraction. In various studies, upregulation of Rho kinase/Rho A protein was linked

to both ED and LUTS.33,34 The relaxant and antiproliferative effects of Rho kinase inhibitors reaffirmed this finding.35 BOO inducing ED via upregulation of Rho kinase was reported in an animal study.36 There is also a possibility that a multisystem dysfunction of Rho kinase exists and leads to both ED and LUTS.37 Selleckchem MAPK Inhibitor Library In human endothelial cells, the Rho kinase pathway inhibited activation of eNOS, resulting in decreased smooth muscle relaxation with resultant BOO leading to LUTS.38 Progesterone An understanding of the pathophysiologic associations between the two disorders is needed to improve the treatment of both disorders. Diffuse atherosclerosis of blood vessels supplying pelvic organs, such as the prostate, penis and bladder is associated

with ED and BPH/LUTS.39 Reduced peak systolic velocity of the cavernous artery is related with LUTS in patients with ED.40 Patient who had two risk factors of atherosclerosis (diabetes mellitus, hypertension, hyperlipidemia, smoking) had a significant higher International Prostate Symptom Score (IPSS) compared to patients with one or no risk factor.41 Another epidemiologic study showed that men with risk factors for vascular disorder are more likely to have a higher IPSS and a lower International Index of Erectile Function (IIEF) score than men without risk factors.42 The alterations of detrusor and corporal smooth muscle induced by pelvic ischemia and hyperlipidemia are very similar. In the atherosclerosis rabbit, fibrosis, smooth muscle atrophy and decreased compliance of the bladder developed by mixture of acute oxidative stress, bladder hypoxia, and concomitant pelvic neurodegeneation.43 Chronic hypoxia is associated with an increased production of profibrotic and proapoptotic cytokines, such as transforming growth factor-b1 (TGF ß1) and small mothers against decapentaplegic (smad).44 These correlate with the severity of fibrosis of the smooth muscle.