Presentation Authors: Yusuke Kimura*, Masashi Honda, Ryo Sasaki, Panagiota Tsounapi, Shuichi Morizane, Katsuya Hikita, Mitsuhiko Osaki, Futoshi Okada, Atsushi Takenaka, Yonago, Japan
Introduction: Circadian rhythms are regulated by clock gene products, and in the case of mammals, these clock gene products are present in most cells and organs. It is reported that transient receptor potential cation channel subfamily V member 4 (TRPV4), vesicular nucleotide transporter (VNUT), and Piezo1 show circadian rhythms in the bladder mucosa and that these circadian rhythms are hindered by clock gene abnormality. However, the effect of bladder clock genes on bladder dysfunction remains unclear. In this study, we investigate the expression and circadian rhythm of TRPV1, TRPV4, VUNT, Piezo1, and clock genes in the bladders of spontaneously hypertensive rats (SHR).
Methods: Male Wistar rats (control group) and male SHRs (SHR group) were used in this study. The experimental animals were placed 12 h of alternating light and dark conditions. Upon completing 18 weeks of age, urination was evaluated using a metabolism gauge (MG). The parameters evaluated included urine volume, urination frequency, and urine volume per void for 24 h, during the light and dark periods, and these parameters were compared between the two groups. After collecting MG data, bladders were harvested every 4 h at six time points from Wistar and SHRs (n = 6 for each time), and the gene expression of Per2, Cry2, Bmal1, Clock, Rev-erbÎ±, TRPV1, TRPV4, VUNT, and Piezo1 was examined using qRT-PCR.
Results: The urination frequency for 24 h, both during the light and dark periods, was significantly higher in the SHR group than in the control group. Urine volume per void was significantly lower in the SHR group than the control group during both light and dark periods. In the control group urine volume per void was significantly lower during the dark than during the light period. However, there was no significant difference in urine volume per void between the light and dark periods in the SHR groups. In the SHR bladders, we observed significant increase in the expression of Per2 and Rev-erbÎ± at all time points and increase in Cry2, Bmal1, and Clock expression in some but not all time points compared to the control group. Expression of TRPV1, TRPV4, VUNT, and Piezo1 were significantly higher during the dark period in the SHR group than in the control group.
Conclusions: Our results suggest that TRPV1, TRPV4, VNUT, and Piezo1 may be involved in the decrease of bladder capacity during the dark period in SHR.