Long-term Nitric Oxide (no) Deficiency Induces Detrusor Overactivity by Increasing Extracellular Ca2+ Influx through L-type Ca2+ Channels

Hypothesis / aims of study Nitric oxide (NO) has been recognized as an important neurotransmitter in the lower urinary tract. Previous studies have shown the presence of NO synthases (NOS) in urothelium and detrusor smooth muscle (DSM) in different animal species. Recently, long-term NO blockade has been shown to cause bladder dysfunction and detrusor overactivity in rats [1,2]. However, the mechanisms by which long-term NO deficiency lead to bladder dysfunction still needs further investigation. This study aimed to characterize the bladder dysfunction in mice treated chronically with the NOS inhibitor N G -nitro-L-arginine methyl ester (LNAME), focusing our attention to the urodynamic alterations, along with the changes in the contractile responses in isolated DSM. Since NO is reported to reduce extracellular Ca 2+ influx through L-type voltage operated Ca 2+ channels (LVOCC) via GMPc/PKG signaling pathway [3], we also investigated the effects of the LVOCC blocker amlodipine in the bladder dysfunction resulting from chronic NO blockade.