Chronic sympathetic nervous system disorder leads to lower urinary tract dysfunction (LUTD) associated with overactive bladder (OAB), but underling mechanisms remain poorly understood. L-γ-glutamylethylamide (L-theanine), a glutamine derivative present in Japanese green tea, has recently gained attention for its sympathetic inhibitory effects. We speculated that L-theanine might suppress the development of LUTD associated with chronic sympathetic hyperactivity. This study therefore examined the effects of L-theanine on LUTD in spontaneously hypertensive rats (SHR), as a rat model of OAB with chronic sympathetic hyperactivity.

Twelve-week-old SHR were divided into a control groups (n=10) and an L-theanine group(n=10) that was given L-theanine solution to drink ad labium. After 6 weeks, both groups underwent cystometry and measurement of blood pressure and plasma catecholamine levels. Bladder tissue was harvested for pharmacological studies, histological examinations, and protein expression analyses. Contractile responses to 80-mM KCl, electrical field stimulation, 1-mM adenosine triphosphate (ATP), and carbachol in organ baths were recorded. As an evaluation of histological changes in the bladder, collagen-to-muscle (C/M) ratio in the smooth muscle layer and tunica media-to -internal lumen (M/L) ratio of small resistance vessels in the submucosal layer were measured. Malondialdehyde (MDA) and hypoxia-inducible factor (HIF)-1α were assessed as biomarkers for oxidative stress using immunohistochemical staining and western blotting. Values of p<0.05 were considered statistically significant.

Bodyweight and bladder wet weights did not differ significantly between control (body weight: 353.0±12.3 g; bladder wet weight: 0.19±0.03 g) and L-theanine groups (354.0±11.3 g, p=0.70; 0.22±0.04 g, p=1.00, respectively). Mean blood pressure was significantly decreased in the L-theanine group (173.3±4.3 mmHg) compared with controls (159.9±3.3 mmHg, p=0.046). Serum noradrenaline level was significantly lower in the L-theanine group (365.5±31.6 pg/ml) than in controls (246.2±34.3 pg/ml, p=0.04). Cystometrograms showed that micturition interval and mean voided volume were significantly larger in the L-theanine group (7.8 ± 1.7 min and 1.3±0.35 ml, respectively) than in controls (5.6±8.4 min, p=0.002 and 0.96±0.18 ml, p=0.03, respectively). Contractile responses of bladder strips were significantly higher in the L-theanine group than in controls. C/M ratio, indicating the degree of fibrosis, was significantly lower in the L-theanine group than in controls (p=0.02). M/L ratio, indicating vascular resistance, was also significantly decreased in the L-theanine group than in controls (p=0.01). Although expression of HIF-1α did not differ significantly between groups, MDA expression was clearly decreased in the L-theanine group (p=0.03).

Our results suggest that ingestion of L-theanine for 6 weeks were effectively preserved lower urinary tract function in SHR. MBP depends on the vascular resistance of small arteries, which are responsible for providing a steady supply of blood to peripheral organs. The decreased MBP, reduced plasma noradrenaline concentrations, and decreased M/L ratio in bladder submucosa suggest that L-theanine suppressed chronic sympathetic hyperactivity and even improved peripheral vascular resistance. The evaluations of oxidative stress markers implied that L-theanine might improve LUTD by inhibiting oxidative stress pathways other than ischemia caused by chronic sympathetic hyperactivity.

L-theanine in Japanese green tea might prevent or ameliorate LUTD caused by chronic sympathetic hyperactivity by inhibiting oxidative stress pathways.