title: Long-term administration of BAY 41-2272 prevents bladder dysfunction in nitric oxide-deficient rats.
abstract: OBJECTIVE
  Chronic blockade of nitric oxide (NO) synthesis leads to detrusor smooth muscle overactivity. This study aimed to evaluate the protective effects of BAY 41-2272, a soluble guanlylate cyclase activator, on changes in cystometric parameters in NO-deficient rats.
  
  
  METHODS
  Rats were divided into the following groups: (a) control, (b) DMSO, (c) N(ω)-nitro-L-arginine methyl ester hydrochrolide (L-NAME), (d) BAY 41-2272 alone, and (e) L-NAME + BAY 41-2272. The NO synthase blocker L-NAME (20 mg/rat/day) was giving in the drinking water concomitantly or not with BAY 41-2272 (10 mg/kg/day, given by gavage).
  
  
  RESULTS
  Chronic L-NAME treatment markedly increased the mean arterial blood pressure (MABP), and co-treatment with BAY 41-2272 nearly reversed L-NAME-induced rise on MABP. Non-void contractions were significantly increased in L-NAME group (0.90 ± 0.1 number/min) compared with either DMSO or control group (0.49 ± 0.1 number/min), which were prevented by co-treatment with BAY 41-2271 (0.56 ± 025 number/min; P < 0.05). The threshold pressure and peak pressure increased by 70% and 44% after chronic L-NAME treatment, while co-treatment with BAY 41-2272 largely attenuated both of these effects (27% and 22% increase, respectively). The frequency of micturition cycles decreased by about of 50% in L-NAME-treated rats compared with control animals, and co-treatment with BAY 41-2272 normalized this parameter.
  
  
  CONCLUSIONS
  Our data show that long-term oral administration of BAY 41-2272 counteracts the bladder dysfunction seen in NO-deficient rats, indicating that restoration of the NO-cGMP pathway by this compound may be of beneficial value to treat bladder symptoms.
authors.affiliation: Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, SP, Brazil. fabiolamonica@terra.com.br
authors.forename: Fabíola Z
authors.initials: FZ
authors.lastname: Mónica
authors.forename: Ricardo
authors.initials: R
authors.lastname: Reges
authors.forename: David
authors.initials: D
authors.lastname: Cohen
authors.forename: Fabio H
authors.initials: FH
authors.lastname: Silva
authors.forename: Gilberto
authors.initials: G
authors.lastname: De Nucci
authors.forename: Carlos A L
authors.initials: CA
authors.lastname: D'Ancona
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000172:deficiency*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011312:Pressure; D011720:Pyrazoles / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects
chemical_list: C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D019331:NG-Nitroarginine Methyl Ester