Nerve-induced release of nitric oxide from the rabbit corpus cavernosum is modulated by cyclic guanosine 3',5'-monophosphate.
Nitric oxide (NO) is a neurotransmitter of the autonomic nerves in the urogenital tract, in particular the release of NO in the cavernous tissue is of importance for maintaining erection. However, the regulation of NO formation in neurons of the corpus cavernosum is poorly understood. Here, we report, that upon electrical stimulation of isolated rabbit corpus cavernosum, NO/NO(2-) was formed and released in a reproducible fashion. The NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester decreased the amount of NO/NO(2-) released to 50+/-18% (P<0.05). The neurotoxin tetrodotoxin diminished the nerve-induced release of NO/NO(2-), to 35+/-10% (P<0.001). Blockage of the cholinergic and noradrenergic pathways by application of scopolamine and guanethidin (both 10(-5) M) did not alter the basal or nerve-evoked formation of NO/NO(2-). We also applied modulators of the soluble guanylate cyclase (sGC)/cyclic guanosine 3',5'-monophosphate (cGMP) pathway to study if and to what extent cGMP might affect the release of NO from the erectile tissue. In the presence of the cGMP analog 8-Br-cGMP (10(-4) M), and, the sGC stimulator 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (10(-4) M), the release of NO/NO(2-) was increased to 385+/-120% (P<0.05) and 282+/-78% (P<0.05), respectively. The effect of the phosphodiesterase inhibitor zaprinast (10(-4) M), was not significant (209+/-53%, n.s). In contrast, inhibition of sGC by 1-H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (10(-5) M) decreased the release of NO/NO(2-) to 64+/-14% (P<0.05). Our results suggest that NO/NO(2-) is released by nitrergic neurons within the rabbit corpus cavernosum and that the release is subject to modulation by the sGC/cGMP pathway, but not to modulation by acetylcholine or noradrenaline.
Hallén
K
K
Department of Surgical Science, Section of Urology, Karolinska Institutet, 171 76 Stockholm, Sweden. katarina.hallen@fyfa.ki.se
Gustafsson
L E
LE
Wiklund
N P
NP
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D010276:Parasympatholytics / Q000494:pharmacology; D010413:Penis / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D011817:Rabbits; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D018680:Cholinergic Antagonists; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D010276:Parasympatholytics; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D013779:Tetrodotoxin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D006162:Guanylate Cyclase; D006152:Cyclic GMP