Effects of the nuclear factor-kappa B inhibitors 2-hydroxy-4-trifluoromethylbenzoic acid and aspirin on micturition in rats with normal and inflamed bladder

Purpose: We examined the effects of intravenous administration of the 2 nuc lear factor-KB inhibitors aspirin and 2-hydroxy-4-trifluoromethylbenzoic ac id (HTB) on bladder filling and voiding in anesthetized and conscious rats. Materials and Methods: Disappearance of isovolumic bladder contractions aft er intravenous administration of different doses of aspirin and HTB in anes thetized, transurethrally catheterized rats was evaluated. Cystometry was p erformed in conscious rats during bladder infusion with saline or diluted a cetic acid as well as in those with cyclophosphamide induced cystitis. Chan ges in bladder capacity and voiding pressure were evaluated after intraveno us administration of test compounds. Results: Aspirin induced a dose dependent disappearance of isovolumic bladd er contractions in anesthetized rats with an extrapolated close of 2.1 mg./ kg. inducing 10 minutes of bladder quiescence. HTB was practically inactive , inducing a dose independent block of 3 to 4 minutes after intravenous adm inistration of 1 to 10 mg./kg. In conscious rats with a bladder infused wit h saline aspirin was poorly active on bladder capacity, inducing a 20% incr ease 60 minutes after intravenous administration of 30 and 100 mg./kg. In r ats with a bladder infused with acetic acid aspirin was much more active wh en injected at the initiation of inflammation and after 1 hour of irritant infusion. In this latter situation aspirin increased bladder capacity up to 60% after intravenous administration of 30 and 100 mg./kg. Similar results were obtained in rats with cyclophosphamide induced cystitis in which the bladder was infused with saline. In these cystometrography models 30 mg./kg . HTB intravenously was completely inactive. Conclusions: The results show that HTB is devoid of significant effects on the micturition reflex in the absence or presence of bladder inflammation, suggesting that acute inhibition of nuclear factor-kappaB does not influenc e bladder urodynamics in rats. In contrast, aspirin, which is a cyclooxygen ase and nuclear factor-kappaB inhibitor, was always effective, indicating t he important role of cyclooxygenase enzymes.