Accumulated endogenous NOS inhibitors, decreased NOS activity, and impaired cavernosal relaxation with ischemia

2002 ◽  
Vol 282 (6) ◽  
pp. R1730-R1738 ◽  
Author(s):  
Hitoshi Masuda ◽  
Toshihiko Tsujii ◽  
Tetsuo Okuno ◽  
Kazunori Kihara ◽  
Moritaka Goto ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Corpus Cavernosum ◽  
Electrical Field Stimulation ◽  
No Synthase ◽  
Field Stimulation ◽  
Electrical Field ◽  
Vessel Occlusion ◽  
Endogenous Inhibitors ◽  
Nos Inhibitors

We examined whether endogenous inhibitors of nitric oxide (NO) synthesis are involved in the impaired cavernosal relaxation with ischemia in rabbits. Two weeks after cavernosal ischemia caused by partial vessel occlusion, endothelium-dependent and electrical field stimulation (EFS)-induced neurogenic NO-mediated relaxations, but not sodium nitroprusside (SNP)-induced relaxation, were significantly impaired in the isolated corpus cavernosum. The Ca2+-dependent NO synthase (NOS) activity and the basal and stimulated cGMP productions with carbachol or EFS were significantly decreased after ischemia. Supplementation of excessl-arginine partially recovered both of the impaired relaxations. The contents of N G-monomethyl-l-arginine (l-NMMA) and asymmetric N G, N G-dimethyl-l-arginine (ADMA) but not l-arginine and symmetric N G, N′G-dimethyl-l-arginine (SDMA) were increased in the cavernosal tissues after ischemia. Authentic l-NMMA and ADMA but not SDMA concentration dependently inhibited both relaxations without affecting the relaxation produced by SNP in the control. Excess l-arginine abolished the inhibition with l-NMMA and ADMA. These results suggest that the impaired NO-mediated cavernosal relaxations after ischemia are closely related to the decreased NOS activity and the increased accumulation of l-NMMA and ADMA.

Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle

1990 ◽  
Vol 170 (2) ◽  
pp. 843-850 ◽  
Author(s):  
Louis J. Ignarro ◽  
Peggy A. Bush ◽  
Georgette M. Buga ◽  
Keith S. Wood ◽  
Jon M. Fukuto ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Cyclic Gmp ◽  
Corpus Cavernosum ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Electrical Field

Inhibitory nerve distribution and mediation of NANC relaxation by nitric oxide in horse airways

1994 ◽  
Vol 76 (1) ◽  
pp. 339-344 ◽  
Author(s):  
M. Yu ◽  
Z. Wang ◽  
N. E. Robinson ◽  
P. H. Leblanc
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Electrical Field Stimulation ◽  
Adrenergic Innervation ◽  
No Synthase ◽  
Field Stimulation ◽  
Electrical Field ◽  
Peripheral Airways ◽  
Synthase Inhibitor ◽  
Nanc Relaxation

The distribution of inhibitory nerves and the mediator of the inhibitory nonadrenergic noncholinergic (iN-ANC) nervous system were investigated in smooth muscle preparations from seven regions of equine airways. In tissues incubated with atropine and precontracted with histamine, electrical field stimulation produced frequency-dependent relaxation, and the magnitude of the relaxation decreased from trachea to central bronchi and was absent in peripheral airways. The degree of relaxation in bronchi was not simply a function of bronchial size or generation. Propranolol inhibited part of the relaxation only in the cranial trachealis. After propranolol, NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, eliminated the remaining relaxation in all preparations. This effect was reversed by L-arginine, the NO precursor, but not by D-arginine. Exogenous NO concentration dependently relaxed trachealis. These results indicate that: 1) adrenergic innervation is limited to cranial trachealis, 2) iNANC nerves supply the trachea and central bronchi, and 3) NO mediates iNANC function.

Nitric Oxide is Involved in the Inhibitory Neurotransmission and Endothelium-Dependent Relaxations of Human Small Penile Arteries

1997 ◽  
Vol 92 (3) ◽  
pp. 269-275 ◽  
Author(s):  
ULF Simonsen ◽  
Dolores Prieto ◽  
Jose Angel Delgado ◽  
Medardo Hernández ◽  
Luis Resel ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Corpus Cavernosum ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Electrical Field ◽  
Small Arteries ◽  
Inhibitory Neurotransmission ◽  
Oxide Synthase ◽  
Penile Arteries

1. Alteration in the flow of blood to the penis is thought to be the most frequent organic cause of erectile dysfunction or impotence. However, information concerning the penile small arteries (helicine arteries) which control blood flow between the arterial systemic circulation and the cavernous sinusoids is scarce. Therefore, the purpose of the present study was to investigate the involvement of nitric oxide, which is considered to be the main neurotransmitter in corpus cavernosum, in both the non-adrenergic non-cholinergic inhibitory neurotransmission and the endothelium-dependent responses in human penile small arteries. 2. Penile small arteries (lumen diameter 200-700 μm), which were branches of the human deep penile arteries obtained either from patients undergoing penile surgery or from organ donors, were mounted in microvascular myographs for isometric tension recording and electrical field stimulation was performed in the presence of guanethidine and atropine to block adrenergic neurotranmission and muscarinic receptors, respectively. 3. In phenylephrine-contracted penile small arteries, electrical field stimulation (0.5–32 Hz) induced frequency-dependent relaxations of both endothelium-intact and -denuded preparations. The inhibitor of nitric oxide synthase, NG-nitro-l-arginine (3 × 10−5 mol/l), abolished the relaxations at the lowest frequencies, while slow-developing relaxations were still observed at high frequencies (16 and 32 Hz). The inhibitory effect of NG-nitro-l-arginine was reversed in the presence of l-arginine (3 × 10−3 mol/l). Tetrodotoxin totally abolished the relaxations to electrical field stimulation. In contracted small penile arteries in the presence of NG-nitro-l-arginine, the nitrovasodilator sodium nitroprusside induced potent relaxations. 4. The endothelium-dependent vasodilator acetylcholine induced relaxations of penile small arteries, which were only partially reduced in the presence of NG-nitro-l-arginine. In contrast, the relaxations to acetylcholine of trabecular corpus cavernosum preparations were almost abolished in the presence of NG-nitro-l-arginine. 5. The present study suggests that relaxations of human intracavernosal small penile arteries induced by non-adrenergic non-cholinergic nerve stimulation partially involve nitric oxide and also another inhibitory transmitter causing relaxations resistant to nitric oxide synthase blockade. In addition, endothelium-dependent relaxations in human small penile arteries are mediated by both nitric oxide and a factor resistant to NG-nitro-l-arginine.

Pharmacologic responses of the mouse urinary bladder

Open Medicine ◽  
2009 ◽  
Vol 4 (2) ◽  
pp. 192-197 ◽  
Author(s):  
A. Canda ◽  
Christopher Chapple ◽  
Russ Chess-Williams
Keyword(s):  
Nitric Oxide ◽  
Urinary Bladder ◽  
Electrical Field Stimulation ◽  
Inhibitory Effect ◽  
Minor Role ◽  
Detrusor Muscle ◽  
Field Stimulation ◽  
Muscarinic Agonists ◽  
Electrical Field ◽  
M3 Receptor

AbstractThe aim of the study was to determine pathways involved in contraction and relaxation of the mouse urinary bladder. Mouse bladder strips were set up in gassed Krebs-bicarbonate solution and responses to various drugs and electrical field stimulation were obtained. Isoprenaline (b-receptor agonist) caused a 63% inhibition of carbachol precontracted detrusor (EC50=2nM). Carbachol caused contraction (EC50=0.3µM), responses were antagonised more potently by 4-DAMP (M3-antagonist) than methoctramine (M2-antagonist). Electrical field stimulation caused contraction, which was inhibited by atropine (60%) and less by guanethidine and α,β-methylene-ATP. The neurogenic responses were not potentiated by inhibition of nitric oxide synthase. Presence of an intact urothelium significantly depressed responses to carbachol (p=0.02) and addition of indomethacin and L-NNA to remove prostaglandin and nitric oxide production respectively did not prevent the inhibitory effect of the urothelium. In conclusion, b-receptor agonists cause relaxation and muscarinic agonists cause contraction via the M3-receptor. Acetylcholine is the main neurotransmitter causing contraction while nitric oxide has a minor role. The mouse and human urothelium are similar in releasing a factor that inhibits contraction of the detrusor muscle which is unidentified but is not nitric oxide or a prostaglandin. Therefore, the mouse may be used as a model to study the lower urinary tract.

Nitric oxide as modulator of cholinergic neurotransmission in gastric muscle of rabbits

1997 ◽  
Vol 273 (2) ◽  
pp. G456-G463 ◽  
Author(s):  
M. C. Baccari ◽  
C. Iacoviello ◽  
F. Calamai
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Substance P ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Electrical Field ◽  
Prostaglandin F2 Alpha ◽  
Fast Relaxation ◽  
Gastric Muscle ◽  
Relaxant Response

The effects of the nitric oxide (NO) synthesis inhibitors, NG-nitro-L-arginine (L-NNA) and NG-nitro-L-arginine methyl ester (L-NAME), on the electrical field stimulation (EFS)-induced inhibitory responses were investigated. EFS caused, in strips contracted by means of substance P (SP), prostaglandin F2 alpha (PGF2 alpha), or carbachol (CCh), a fast relaxant response that, depending on stimulation frequency and strip tension, could be followed by a slower, sustained relaxation. The NO synthesis inhibitors blocked the EFS-induced fast relaxations and often reversed them into contractions; these effects were greatly counteracted in SP- or PGF2 alpha-treated strips by scopolamine or atropine. In CCh-precontracted strips, either L-NNA or L-NAME became progressively unable to block the EFS-induced fast relaxations as the CCh concentration was increased. The NO synthesis inhibitors greatly reduced the sustained relaxant responses elicited either by EFS or exogenous vasoactive intestinal polypeptide (VIP). The results indicate that the NO synthesis inhibitors abolish the neurally induced fast relaxation by interfering with the cholinergic excitatory pathway. The involvement of both VIP and NO in sustained relaxations is also suggested.

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