[In vitro effects of a novel class of nitric oxide donating compounds on isolated human urinary bladder].
Nitric oxide (NO) has been identified an important neurotransmitter involved in the control of the human urinary tract. It has been suggested that NO is one of the factors keeping the bladder relaxed during the filling phase. This function might be mediated by the NO-induced elevation of intracellular cyclic GMP. Prostaglandins (PG) are known to exert contractile effects on the bladder smooth musculature, especially in pathological conditions. The aim of the present study was to examine the effects of a new class of NO donor drugs, combining both anti-phlogistic and NO-donating activity (NCX 2111 and HCT 1026), on the contraction induced by PG or electrical field stimulation (EFS) of isolated human detrusor. Effects were compared to those of sodium nitroprusside (SNP), forskolin, tolterodine, and oxybutynin. Using the organ bath technique, drug effects on the contraction induced by PG ((F2 alpha)) or EFS of isolated human detrusor smooth muscle were investigated. Detrusor strips were also exposed to increasing concentrations of the compounds (0.1 microM - 10 microM) and the accumulation of cyclic GMP and cyclic AMP was determined by means of radioimmunoassays. The tension induced by PG was dose-dependently reversed by the drugs. The rank order of efficacy was: forskolin > SNP > NCX 2111 > HCT 1026. R(max) values ranged from 57% (forskolin) to 24% (HCT 1026). Compounds also dose-dependently reduced the amplitudes of contraction induced by EFS (tolterodine > oxybutynin > NNP = forskolin > HCT 1026 > 2111). The effects of forskolin, HCT 1026, NCX 2111 and SNP were paralleled by an increase in cyclic AMP or cyclic GMP. Our results provide evidence that the NO-cGMP pathway is not of utmost significance in the control of human detrusor smooth muscle. In vitro, the combination of NO-donating with anti-phlogistic activity does not seem to be of functional advantage with regard to the facilitation of detrusor relaxation.
Kedia
G T
GT
Hannover Medical School, Department of Urology and Uro-Oncology, Hannover, Germany.
Neumayer
E
E
Scheller
F
F
Kuczyk
M A
MA
Uckert
S
S
D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006152:Cyclic GMP / Q000378:metabolism; D005480:Flurbiprofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000890:Anti-Infective Agents; C095631:nitroflurbiprofen; D009569:Nitric Oxide; D005480:Flurbiprofen; D006152:Cyclic GMP