Nitric oxide modulates bladder afferent nerve activity in the in vitro urinary bladder-pelvic nerve preparation from rats with cyclophosphamide induced cystitis.
Effects of a nitric oxide (NO) donor (SNAP), NO substrate (l-arginine), and NO synthase inhibitor (l-NAME) on bladder afferent nerve (BAN) activity were studied in an in vitro bladder-pelvic nerve preparation from untreated or cyclophosphamide (CYP) treated rats. Distension of the bladder induced phasic bladder contractions (PBC) that were accompanied by multiunit afferent firing. Intravesical administration of SNAP (2mM) which did not change the amplitude of PBC significantly decreased peak afferent firing from 79 ± 15 spikes/s to 44 ± 8 spikes/s in CYP pretreated but not untreated preparations. In CYP treated preparations SNAP also decreased by 33-55% BAN firing induced by isotonic distension of the bladder at 10-40 cmH(2)O pressures. Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. SNAP significantly increased the voltage threshold by 75% (p<0.05) and decreased by 45% (p<0.05) the area of the AP evoked at submaximal stimulus intensity. Bath application of SNAP (2mM) or l-arginine (50mM) elicited similar inhibitory effects on the distension evoked BAN firing. The effects of l-arginine were blocked by bath application of l-NAME (20mM). l-NAME alone did not alter BAN firing. In preparations from normal rats SNAP or l-arginine did not alter BAN activity. These results suggest that exogenous as well as endogenously generated NO depresses the excitability of sensitized but not normal BAN and that NO may have an antinociceptive function and modulate bladder hyperactivity induced by pathological conditions.
Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA. yyu@pitt.edu
Yongbei
Y
Yu
William C
WC
de Groat
D000200:Action Potentials / Q000187:drug effects; D000477:Alkylating Agents; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced* / Q000503:physiopathology*; D003627:Data Interpretation, Statistical; D055724:Electrophysiological Phenomena / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007267:Injections; D007551:Isotonic Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D010525:Peripheral Nerves / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D001743:Urinary Bladder / Q000294:innervation* / Q000502:physiology*
D000477:Alkylating Agents; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D003520:Cyclophosphamide; D001120:Arginine; D052248:Nitric Oxide Synthase Type I; D019331:NG-Nitroarginine Methyl Ester