title: Chronic Pelvic Ischemia: Contribution to the Pathogenesis of Lower Urinary Tract Symptoms (LUTS): A New Target for Pharmacological Treatment?
abstract: The incidence of lower urinary tract symptoms, including overactive bladder (OAB), is continuing to rise, and is associated with a negative impact on quality of life and a heavy economic burden. A major risk factor for OAB is advancing age. The etiology of OAB is multifactorial and appears to involve myogenic, neurogenic, and urotheliogenic factors. In this article, we review the strengthening preclinical evidence supporting the contribution of chronic pelvic ischemia to the pathogenesis of OAB. In animal models, chronic ischemia induced by arterial injury and a high-fat diet upregulates markers of oxidative stress and proinflammatory cytokines in the urothelium and lamina propria, and leads to increased expression of nerve growth factor. These processes result in increased afferent activity and an increased frequency of micturition, reflecting a state of bladder hyperactivity. In severe, prolonged cases, bladder overactivity may develop into underactivity. Antimuscarinic therapies are the mainstay of OAB treatment, but their usefulness is limited by modest efficacy and troublesome side-effects. Our increasing understanding of the contribution of chronic ischemia to OAB is leading toward novel therapeutic options targeting chronic pelvic ischemia and its morphological, functional, and oxidative consequences. Preclinical trials have demonstrated encouraging results with α1 -adrenoreceptor blockade, phosphodiesterase type 5 inhibition, β3 -adrenoreceptor agonism, free radical scavenging, and stem cell therapy, in preventing morphological, biochemical and functional changes induced by chronic bladder ischemia.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.affiliation: Division of Bioengineering and Lower Urinary Tract Diseases Research, Nihon University School of Engineering, Koriyama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomiya
authors.affiliation: Division of Bioengineering and Lower Urinary Tract Diseases Research, Nihon University School of Engineering, Koriyama, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000627:therapeutic use; D058673:Adrenergic beta-3 Receptor Antagonists / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D007511:Ischemia / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D059411:Lower Urinary Tract Symptoms / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D010388:Pelvis / Q000098:blood supply*; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D058673:Adrenergic beta-3 Receptor Antagonists; D016166:Free Radical Scavengers; D058986:Phosphodiesterase 5 Inhibitors
keywords: chronic pelvic ischemia; overactive bladder