Introduction: Chronic sympathetic hyperactivity had been reported as a factor of lower urinary tract dysfunction (LUTD), but little is known about the mechanisms. L-?-glutamylethylamide (L-theanine), one of the glutamine derivatives in Japanese green tea, has recently focused on the sympathetic inhibitory effects. Hence, we speculated that L-theanine might suppress the development of LUTD associated with chronic sympathetic hyperactivity. This study aimed to clarify the mechanisms underlying the effect of L-theanine on LUTD in spontaneously hypertensive rats (SHR) known as one of OAB rat models with chronic sympathetic hyperactivity. Methods: Twelve-week-old SHR were divided into two groups (controls, n=10; L-theanine, n=10). The L-theanine group was given only L-theanine solution to drink freely. After six weeks, blood pressure, plasma catecholamine level measurement, and cystometry were performed in both groups. The bladder tissue was harvested for pharmacological studies, histological examinations, and protein expression analysis. Contractile responses to 80-mM KCl, electrical field stimulation, 1-mM ATP, and carbachol in organ baths were recorded. Malondialdehyde (MDA), biomarkers for oxidative stress, was assessed using immunohistochemical staining and Western blotting. Values of p<0.05 were considered statistically significant. Results: There was no significant difference in systolic and diastolic blood pressure between two groups. Mean blood pressure was significantly lower in the L-theanine group than in controls (p=0.046). The plasma 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). The cystometrogram showed the micturition interval and mean voided volume were significantly larger in the L-theanine group (7.8 ± 1.7 min, 1.3 ± 0.35 ml) than in controls (5.6 ± 8.4 min, 0.96 ± 0.18 ml, p=0.002, p=0.03). Contractile responses of bladder strip were significantly higher in the L-theanine group than in controls. The collagen/muscle ratio of the bladder smooth muscle was significantly decreased in the L-theanine group (p=0.02). The expression of MDA was significantly decreased in the L-theanine group (p < 0.001). Conclusions: These results suggested that L-theanine ameliorated excessive contraction of vascular smooth muscle in peripheral small arteries by suppressing elevated serum levels of noradrenaline in SHR, thereby decreasing MBP. Oral administration of L-theanine for 6 weeks may contribute to the prevention of bladder voiding function, along with storage function by increasing blood perfusion in the bladder. SOURCE OF Funding: Nothing
