Effects of nitric oxide inhibitors in mice with bladder outlet obstruction.
OBJECTIVE
To investigate the lower urinary tract changes in mice treated with L-NAME, a non-selective competitive inhibitor of nitric oxide synthase (NOS), or aminoguanidine, a competitive inhibitor of inducible nitric oxide synthase (iNOS), after 5 weeks of partial bladder outlet obstruction (BOO), in order to evaluate the role of constitutive and non-constitutive NOS in the pathogenesis of this experimental condition.


METHODS
C57BL6 male mice were partially obstructed and randomly allocated into 6 groups: Sham, Sham + L-NAME, Sham + aminoguanidine, BOO, BOO + L-NAME and BOO + aminoguanidine. After 5 weeks, bladder weight was obtained and cystometry and tissue bath contractile studies were performed.


RESULTS
BOO animals showed increase of non-voiding contractions (NVC) and bladder capacity, and also less contractile response to Carbachol and Electric Field Stimulation. Inhibition of NOS isoforms improved bladder capacity and compliance in BOO animals. L-NAME caused more NVC, prevented bladder weight gain and leaded to augmented contractile responses at muscarinic and electric stimulation. Aminoguanidine diminished NVC, but did not avoid bladder weight gain in BOO animals and did not improve contractile responses.


CONCLUSIONS
It can be hypothesized that chronic inhibition of three NOS isoforms in BOO animals leaded to worsening of bladder function, while selective inhibition of iNOS did not improve responses, what suggests that, in BOO animals, alterations are related to constitutive NOS.
Departamento de Cirurgia, Faculdade de Ciências Médicas - UNICAMP, Campinas, SP, Brasil.
Marcy Lancia
ML
Pereira
Departamento de Urologia, Faculdade de Ciências Médicas - UNICAMP, Campinas, SP, Brasil.
Carlos Arturo Levi
CA
D'ancona
Departamento de Farmacologia, Faculdade de Ciências Médicas - UNICAMP, Campinas, SP, Brasil.
Julio Alejandro
JA
Rojas-Moscoso
Departamento de Farmacologia, Faculdade de Ciências Médicas - UNICAMP, Campinas, SP, Brasil.
Antonio Celso Saragossa
AC
Ramos
Departamento de Farmacologia, Faculdade de Ciências Médicas - UNICAMP, Campinas, SP, Brasil.
Fabiola Zakia
FZ
Monica
Departamento de Farmacologia, Faculdade de Ciências Médicas - UNICAMP, Campinas, SP, Brasil.
Edson
E
Antunes
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D059411:Lower Urinary Tract Symptoms / Q000188:drug therapy*; D008297:Male; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011312:Pressure; D011897:Random Allocation; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000503:physiopathology; D014554:Urination / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D006146:Guanidines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester
NG-Nitroarginine Methyl Ester; Nitric Oxide; Urinary Bladder