salicylates and Cystitis

We examined the effects of intravenous administration of the 2 nuclear factor-kappaB inhibitors aspirin and 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) on bladder filling and voiding in anesthetized and conscious rats.. Disappearance of isovolumic bladder contractions after intravenous administration of different doses of aspirin and HTB in anesthetized, transurethrally catheterized rats was evaluated. Cystometry was performed in conscious rats during bladder infusion with saline or diluted acetic acid as well as in those with cyclophosphamide induced cystitis. Changes in bladder capacity and voiding pressure were evaluated after intravenous administration of test compounds.. Aspirin induced a dose dependent disappearance of isovolumic bladder contractions in anesthetized rats with an extrapolated dose 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 administration of 1 to 10 mg./kg. In conscious rats with a bladder infused with saline aspirin was poorly active on bladder capacity, inducing a 20% increase 60 minutes after intravenous administration of 30 and 100 mg./kg. In rats with a bladder infused with acetic acid aspirin was much more active when 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.. 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 influence bladder urodynamics in rats. In contrast, aspirin, which is a cyclooxygenase and nuclear factor-kappaB inhibitor, was always effective, indicating the important role of cyclooxygenase enzymes.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cyclooxygenase Inhibitors; Cystitis; Female; Male; NF-kappa B; Rats; Rats, Sprague-Dawley; Salicylates; Urination; Urodynamics

Our laboratory reported previously the in vivo absorption of salicylate and antipyrine from the urinary bladder of healthy rats. The present study extends these findings to examine the effect of interstitial cystitis on bladder permeability to drugs by comparing the bladder absorption of salicylate in healthy cats and cats with feline interstitial cystitis (FIC). Interstitial cystitis is a lower urinary tract disease and may involve inflammation of the bladder. A 25-mg/kg dose of sodium salicylate was instilled into the bladder and a 6-micrograms/kg i.v. dose of [14C]salicylic acid was administered concomitantly to determine systemic clearance in individual animals. In healthy and FIC cats, the clearance was 0.3 and 0.1 ml.min-1.kg-1, and the bioavailability of the intravesical dose was about 1 and 9%, respectively. The apparent bladder absorption rate constant and the peak plasma concentration in FIC cats were 7 to 8 times that in healthy cats. These data indicate a significantly higher bladder permeability to salicylate due to interstitial cystitis. In order to elucidate the cause of the lower clearance in FIC cats, a second study compared the disposition of a 2-mg/kg i.v. dose of salicylate in healthy and FIC cats. It was found that the lower salicylate clearance in FIC cats was due in part to a decreased metabolism in the disease state and also involved slower drug elimination at the higher plasma concentrations secondary to the more extensive absorption of the intravesical dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Absorption; Animals; Cats; Cystitis; Female; Male; Salicylates; Salicylic Acid; Urinary Bladder

Topics: Adolescent; Adult; Aged; Antibodies, Antinuclear; Antimalarials; Biopsy; Cystitis; Cystoscopy; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Middle Aged; Salicylates; Urine

Topics: Cystitis; Humans; Methenamine; Plants; Salicylates