Experimental Studies On Effect Of Nitric Oxide On Urethral Sphincter's Function And It's Clincal Significance

Objective To explore the effect of nitric oxide on the urethral sphincter's function,to provide theory evidence for that nitric oxide donors could be a new pharmacological approach to treat the bladder outlet obstruction caused by urethral sphincter overactive and non-relaxant. Method The NO concentration in urethral sphincter was monitored by the nitric oxide sensor. Cystometry was studied with WEIST8000 urine dynamic instrument, during cystometry, the detrusor pressures were continuously recorded untill the urine flowed out the external orifice of urethra ,then the bladder capacity was recorded. After the cystometry,emptying the bladder with a syringe,catherising a 8 French three channel pressure transducer to bladder, the urethral pressure profile was performed.The maximum urethral pressure and maximum urethral close pressure was recorded. The heart rate and blood pressure were monitored continuously. Twenty-four healthy adult male crossbreed dogs were used in the study .They were divided into 3 groups,according to whether or not given L-NAME (non-selective nitric oxide synthase inhibitor and the doses, Group A NO donsor, isosorbide dinitrate 5mg, group B1 L-NAME10mg/kg, group B2, L-NAME20mg/kg. The blood pressure(BP), heart rate(HR),the maximum urethral pressure(MUP) and the maximum urethral close pressure(MUCP), NO concentration, bladder capacity(BC), detrusor pressures were compared before and after administration by analysis of variance for repeated measurement(level of significance P<0.05). Result Group A After administration of isosorbide dinitrate 5mg , the NO concentration in urethral sphincter increased,especially after 20 minutes .The MUP and MUCP decreased , especially after 20 minutes , compared with before administration (P<0.05). Group B1 and group B2 After administration of L-NAME, the NO concentration in urethral sphincter decreased,especially after 30 minutes, the MUP and MUCP increased, especially after 30 minutes , compared with before administration (P<0.05). The difference of MUP and MUCP between group B1 and group B2, was statistical significance (P<0.05). The difference of BC and DP before and after the administration were not statistically significant difference (P>0.05) in group A and group B1. The BC only decreased significantly 30minutes after administration than before in Group B2(P<0.05). The DP increased significantly(P<0.05) only 30minutes after administration than before in Group B2. Conclusion NO can relax the urethral sphincter in dog. NO donor could be used to reduce the pressure in urethral sphincter. NOS inhibitors can reduce the NO concentration in urethral sphincter and inhibit the relaxation of the urethral sphincter, increase MUP and MUCP. Nitric oxide donor could be a new pharmacological approach to treat the bladder outlet obstruction caused by urethral sphincter overactive and non-relaxant.