Abstract
The functional role of nitric oxide (NO) and the guanylate cyclase/cGMP second messenger system was investigated in the mouse bladder. Electrical field stimulation and the NO-donor 3-morpholino-sydnonimin hydrochloride (SIN-1) did not induce relaxation of the carbachol-precontracted bladder. However, sodium nitroprusside (10(-3) M) was found to enhance the contractile response to electrical field stimulation by 24+/-6% (n=8; P<0.05) without affecting the contractile response to carbachol. The enhancement of bladder contractility evoked by sodium nitroprusside was inhibited by the guanylate cyclase inhibitor 1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalime-1-one (ODQ; 10(-6) M). Incubation of bladder strips with SIN-1 and sodium nitroprusside caused an increase in cGMP accumulation as measured by radioimmunoassay. Immunohistochemical studies showed cGMP-immunoreactivity in nerve fibres and in stromal cells, but not in smooth muscle bundles after exposure to NO-donors. The results show that NO-donors have no inhibitory effect on smooth muscle tone in the mouse bladder, but that NO may have a functional role as an excitatory neuromodulator. The targets of endogenous NO in the bladder may be the demonstrated cGMP-positive structures, i.e., nerves and stromal cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arginine / pharmacology
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Carbachol / pharmacology
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Cyclic AMP / metabolism
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Cyclic GMP / analogs & derivatives
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Cyclic GMP / metabolism*
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Cyclic GMP / pharmacology
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Dose-Response Relationship, Drug
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Electric Stimulation
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Enzyme Inhibitors / pharmacology
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Female
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In Vitro Techniques
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Mice
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Mice, Inbred BALB C
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Molsidomine / analogs & derivatives
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Molsidomine / pharmacology
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Muscle Relaxation / drug effects*
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Muscle, Smooth / drug effects*
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Muscle, Smooth / physiology
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Nitric Oxide Donors / pharmacology*
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitroarginine / pharmacology
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Nitroprusside / pharmacology
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Phosphodiesterase Inhibitors / pharmacology
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Piperazines / pharmacology
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Piperidines / pharmacology
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Purines
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Quinazolines / pharmacology
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Sildenafil Citrate
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Sulfones
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Urethra / drug effects
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Urethra / metabolism
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Urethra / physiology
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Urinary Bladder / drug effects*
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Urinary Bladder / metabolism
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Urinary Bladder / physiology
Substances
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E 4021
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Enzyme Inhibitors
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Nitric Oxide Donors
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Phosphodiesterase Inhibitors
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Piperazines
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Piperidines
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Purines
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Quinazolines
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Sulfones
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Nitroprusside
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Nitroarginine
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8-bromocyclic GMP
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linsidomine
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Carbachol
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Arginine
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Sildenafil Citrate
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Molsidomine
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Cyclic AMP
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Nitric Oxide Synthase
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Cyclic GMP