Roles of accumulated endogenous nitric oxide synthase inhibitors and decreased nitric oxide synthase activity for impaired trigonal relaxation with ischemia.
OBJECTIVE
We examined whether endogenous nitric oxide (NO) synthase (NOS) inhibitors are involved in the impaired trigonal relaxation with ischemia in rabbits.


METHODS
Rabbits were divided into control and ischemia groups. Two weeks after partial vessel occlusion strips of trigone and detrusor were processed to determine endogenous methylarginines and L-arginine by automated high performance liquid chromatography. We also compared NOS activity and NO mediated functional responses to electrical field stimulation between 2 groups.


RESULTS
Neurogenic and NO but not sodium nitroprusside induced mediated relaxation in the trigone were significantly impaired following ischemia. Ca2+ dependent NOS activity, and baseline and stimulated cyclic guanosine monophosphate production with electrical field stimulation were significantly decreased following ischemia. The contents of L-NMMA (NG-monomethyl-L-arginine) and asymmetrical ADMA (NG, NG-dimethyl-L-arginine) but not L-arginine or symmetrical SDMA (NG, N'G-dimethyl-L-arginine) were increased in the trigone following ischemia. Authentic L-NMMA and ADMA but not SDMA inhibited neurogenic relaxations in a concentration dependent manner without affecting the relaxation produced by sodium nitroprusside in control tissue. Excess L-arginine abolished L-NMMA and ADMA inhibition.


CONCLUSIONS
These results suggest that impaired NO mediated trigonal relaxation following ischemia is closely related to decreased NOS activity and the increased accumulation of L-NMMA and ADMA.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004558:Electric Stimulation; D007511:Ischemia / Q000201:enzymology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D001743:Urinary Bladder / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology*; D019323:omega-N-Methylarginine / Q000378:metabolism
D009599:Nitroprusside; D019323:omega-N-Methylarginine; C024917:symmetric dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase