title: The influence of piroxicam, a non-selective cyclooxygenase inhibitor, on autonomic nervous system activity in experimental cyclophosphamide-induced hemorrhagic cystitis and bladder outlet obstruction in rats.
abstract: Signs and symptoms of secondary overactive bladder (OAB) are observed both in course of infravesical obstruction of urine outflow in patients with benign prostatic hyperplasia, and as a result of development of hemorrhagic cystitis (HC) following administration of cyclophosphamide (CP). Non-steroidal antiinflammatory drugs (NSAIDs) alleviate symptoms of bladder overactivity reducing local synthesis of prostaglandins (PGs), but precise effects of those agents on functions of the autonomic nervous system (ANS) in course of OAB remain unknown. The purpose of this study was to evaluate the effect of piroxicam-induced prostaglandins (PGs) synthesis block on activity of the ANS in two experimental models of secondary OAB: bladder outlet obstruction (BOO) and cyclophosphamide-induced HC (CP-HC), by heart rate variability analysis (HRV). The experiment was performed on a group of rats with surgically induced 2-week BOO, and on a group of rats that were administered CP five times, with corresponding control groups. Study animals were given piroxicam (PRX) i.p. in two doses: 2 and 10 mg/kg b.w. In the BOO model, PRX in both doses revealed a trend for reduction of value of all non-normalized components of HRV. The lower PRX dose caused an increased nHF value, and PRX administered in the dose of 10 mg/kg b.w. caused an increase of the nLF value. In the CP-HC model, the lower PRX dose caused a trend for an increase of values of all non-normalized components, and the higher dose--for their decrease. Both doses of PRX in that model caused increase of the nLF value. Inhibition of PGs synthesis caused changes of ANS function in both models of OAB. Both in BOO and in CP-HC, PGs seem to be ANS-activating factors, responsible for maintenance of a high parasympathetic activity. In both models, inhibition of PGs synthesis with PRX administered at the dose of 10 mg/kg b.w. lead to functional reconstruction of ANS, with marked sympathetic predominance. That may contribute to reduction of the bladder contractile action and improvement of its compliance in the filling period, which was demonstrated by other authors in urodynamic tests for NSAIDs.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Dobrek
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Baranowska
authors.forename: Beata
authors.initials: B
authors.lastname: Skowron
authors.forename: Piotr J
authors.initials: PJ
authors.lastname: Thor
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010894:Piroxicam / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation*; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects
chemical_list: D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D010894:Piroxicam; D003520:Cyclophosphamide