Nitric oxide-induced cGMP accumulation in the mouse bladder is not related to smooth muscle relaxation.
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.
Fujiwara
M
M
Department of Clinical Pharmacology, Lund University Hospital, S-221 85, Lund, Sweden.
Andersson
K
K
Persson
K
K
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011687:Purines; D011799:Quinazolines / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones; D014521:Urethra / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
C091517:E 4021; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D010880:Piperidines; D011687:Purines; D011799:Quinazolines; D013450:Sulfones; D009599:Nitroprusside; D019335:Nitroarginine; C016276:8-bromocyclic GMP; C002385:linsidomine; D002217:Carbachol; D001120:Arginine; D000068677:Sildenafil Citrate; D008981:Molsidomine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP