Intramural Blood Vessels as a Primary Site of Vascular LUTS

Ischaemia has been considered a primary cause of lower urinary tract symptoms (LUTS). The existing concept is that ischaemic LUTS develops subsequent to structural narrowing of feeder arteries of the LUT due to atherosclerosis. However, the distribution of blood flow within each LUT organ that is regulated by intramural microvasculature should also be considered. Thus, the blood supply of the mucosal and detrusor smooth muscle (DSM) in the bladder and the blood flow of the mucosal, smooth muscle and striated muscle in the urethra need to be adjusted to meet their differing energy consumption. Sympathetic overdrive that is commonly seen in aged populations and patients with metabolic syndrome enhances arteriolar constrictions resulting in a disturbed intramural flow distribution so that cell populations with a higher energy demand are more readily affected. In addition to endothelial nitric oxide (NO) that plays a pivotal role in regulating vasocontractility, NO released from perivascular parasympathetic nerves appears to counteract sympathetic activity (sympatholysis) in the LUT. Thus, any diminished neuronally released NO would cause sympathetic overactivity. Capillary rarefaction, the reduced density/function of capillaries, the site of blood-tissue exchange, would also be critically involved in the pathogenesis of LUTS. In the bladder, capillary pericytes appear to function as pacemaker cells driving arteriolar vasomotion facilitating capillary perfusion and may also play a role in maintaining suburothelial homeostasis. Considering the fundamental roles of the intramural microvasculature in maintaining LUT functions, enhanced NO-mediated sympatholysis and/or capillary revascularization could have therapeutic and preventive potential for the ischaemic LUT.