Functional role of inhibitory and excitatory nerves in the porcine lower urinary tract.
In the trigone (three portions) and proximal urethra isolated from castrated male pigs, transmural electrical stimulation (0.5-10 Hz) induced no or slight contractions followed by frequency-related relaxations. Atropine suppressed the contraction and potentiated the relaxation. N(G)-nitro-L-arginine methylester (L-NAME), a nitric oxide (NO) synthase inhibitor, depressed or abolished the relaxation induced by low frequency stimulation, but only slightly attenuated the response to high frequency stimulation. L-Arginine reversed the inhibitory effect. L-NAME-sensitive relaxation by 1 Hz stimulation was abolished by 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. Release of NO by nerve stimulation to trigonal strips was determined by increased formation of cyclic GMP in the incubation media containing guanylate cyclase and GTP. L-NAME-resistant relaxation by 10 Hz stimulation was not impaired by ODQ, capsaicin, chymotrypsin, K(+) channel inhibitors and beta-adrenoceptor antagonists. Similar results were obtained in the trigone and urethra from normal male and female pigs. Detrusor muscle responded to nerve stimulation with contraction followed by slight relaxation. Relaxations at 1 and 10 Hz stimulation under treatment with atropine and alpha,beta-methylene ATP were partially attenuated by L-NAME. It is concluded that there is no significant difference in the inhibitory responses, sensitive and resistant to L-NAME, to nerve stimulation in the trigone and proximal urethra from castrated and non-castrated male and female pigs. Relaxations to stimulation at 1 Hz seem to be mediated exclusively by neurogenic NO and cyclic GMP generation, whereas those to 10 Hz stimulation is mainly associated with non-NO relaxing factor(s), peptides, K(+) channel openers and beta-adrenoceptor agonist being unlikely involved.
Noda
Kumiko
K
Research Laboratories, Nippon Shinyaku Co., Ltd., 14 Nishinosho-Monguchi-cho, Kisshoin, Minami, Kyoto, Japan.
Takebe
Mika
M
Oka
Michiko
M
Hirouchi
Masaaki
M
Ukai
Yojiro
Y
Toda
Noboru
N
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010208:Papaverine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology; D014521:Urethra / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D014551:Urinary Tract / Q000187:drug effects* / Q000294:innervation* / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D015016:Yohimbine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D001285:Atropine; D001120:Arginine; D010208:Papaverine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester; D011224:Prazosin