Influence of Endothelial Nitric Oxide on Adrenergic Contractile Responses of Human Cerebral Arteries

1996 ◽  
Vol 16 (4) ◽  
pp. 623-628 ◽  
Author(s):  
Martín Aldasoro ◽  
Carmen Martínez ◽  
José M. Vila ◽  
Pascual Medina ◽  
Salvador Lluch
Keyword(s):  
Nitric Oxide ◽  
Contractile Response ◽  
Cerebral Arteries ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Oxide Formation ◽  
Electrical Field ◽  
Contractile Responses ◽  
Nitric Oxide Formation ◽  
Endothelial Nitric Oxide

The present study was designed to investigate the influence of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human cerebral arteries to electrical field stimulation (EFS) and norepinephrine. Rings of human middle cerebral artery were obtained during autopsy of 19 patients who had died 3–8 h before. EFS (1–8 Hz) induced frequency-dependent contractions that were abolished by tetrodotoxin, prazosin, and guanethidine (all at 10-6 M). The increases in tension were of greater magnitude in arteries denuded of endothelium. NG-monomethyl L-arginine (L-NMMA 10-4 M) potentiated the contractile response to EFS in artery rings with endothelium but did not influence responses of endothelium-denuded arteries. L-arginine (10-4 M) reversed the potentiating effects of L-NMMA on EFS-induced contractions. Norepinephrine induced concentration-dependent contractions, which were similar in arteries with and without endothelium or in arteries treated with L-NMMA. Indomethacin (3 × 10−6 M) had no significant effect on the contractile response to EFS or on the inhibition by L-NMMA of acetylcholine-induced relaxation. These results suggest that the contractile response of human cerebral arteries to EFS is modulated by nitric oxide mainly derived from endothelial cells; although adrenergic nerves appear to be responsible for the contraction, the transmitter involved in the release of nitric oxide does not appear to be norepinephrine. The effects of L-NMMA in this preparation appear to be due to inhibition of nitric oxide formation rather than caused by cyclooxygenase activation.

scholarly journals Nitric Oxide Mediates the Neurogenic Vasodilation of Bovine Cerebral Arteries

1991 ◽  
Vol 11 (3) ◽  
pp. 366-370 ◽  
Author(s):  
Carmen Gonzalez ◽  
Carmen Estrada
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Nerve Stimulation ◽  
Cerebral Arteries ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Electrical Field ◽  
Muscarinic Receptor Antagonists ◽  
Stimulation Of

Nitric oxide (NO) is a mediator of the vasodilation induced by a variety of physiological and pharmacological stimuli. The possible role of NO in the relaxation elicited in cerebral arteries by perivascular nerve stimulation has been investigated. Electrical field stimulation of precontracted bovine cerebral arteries induced a relaxation that was blocked by tetrodotoxin, but not by adrenergic or muscarinic receptor antagonists, suggesting the existence of nonadrenergic, noncholinergic dilator nerves, as has been shown in other species. The relaxation was significantly reduced by the inhibitors of NO synthesis, NG-monomethyl-L-arginine and nitro-L-arginine methyl ester, but not by the enantiomer, NG-monomethyl-D-arginine. Such a reduction was reversed by L-arginine. In addition, transmural nerve stimulation (TNS)-induced relaxation was potentiated by superoxide dismutase. No response to TNS was observed in arteries without endothelium. These results suggested that neurogenic relaxation of bovine cerebral arteries is mediated by endothelium-derived NO.

Neurokinin (NK2) receptors mediate nonadrenergic noncholinergic contractile responses to electrical stimulation and resiniferatoxin in guinea pig trachea

1994 ◽  
Vol 72 (2) ◽  
pp. 182-188 ◽  
Author(s):  
Luc Charette ◽  
Denise Foulon ◽  
Ian W. Rodger ◽  
Thomas R. Jones
Keyword(s):  
Electrical Stimulation ◽  
Guinea Pig ◽  
Receptor Antagonist ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Large Degree ◽  
Field Stimulation ◽  
Electrical Field ◽  
Nitric Oxide Synthase Inhibitor ◽  
Contractile Responses

In the present study we characterized the receptor(s) that mediates non-adrenergic non-cholinergic (NANC) contractions of isolated guinea pig cervical trachea, using CP-99,994, a selective neurokinin (NK1) receptor antagonist, and SR-48,968, a selective neurokinin (NK2) receptor antagonist. The activity of these two antagonists was determined against contractions to the selective agonists ([βAla8]NKA(4–10) for NK2 and [Sar9,Met(O2)11]SP for NK1) and the nonselective (SP and NKA) NK receptor agonists. CP-99,994 was inactive versus NKA and [βAla8]NKA(4–10) but antagonized SP- and [Sar9,Met(O2)11]SP-induced contractions with −log KB values of 5.6 ± 0.2 and 7.7 ± 0.2, respectively. SR-48,968 was inactive versus SP and [Sar9,Met(O2)11]SP but was active versus NKA and [βAla8]NKA(4–10), yielding −log KB values of 8.4 ± 0.2 and 9.1 ± 0.2, respectively. In the presence of 1 μM atropine, 1.4 μM indomethacin, 0.2 μM timolol, and 4 μM thiorphan, electrical field stimulation (16 Hz, 2.0 ms, 50 V for 10 every 30 min) elicited a NANC contractile response which was not significantly altered by CP-99,994 (3 μM) or the nitric oxide synthase inhibitor L-NAME (10 μM) but was completely inhibited by tetrodotoxin (TTX) (1 μM) and was also reduced to 58 ± 12, 31 ± 16, 8 ± 4, and 0% of control by 15, 50, 150, and 1500 nM SR-48,968, respectively. Resiniferatoxin (1 and 10 nM) produced a well-maintained concentration-dependent contraction, which was 57.8 ± 4.8 and 61.6 ± 3.8%, respectively, of the carbachol-induced maximum response. Contractions were not significantly modified by L-NAME and were not blocked by TTX (1 μM). SR-48,968 (150 nM) almost completely blocked the contractile response to 1 and 10 nM resiniferatoxin. CP-99,994 (0.3 μM) was inactive when tested alone but blocked the residual response in the presence of SR-48,968. It is concluded that TTX-sensitive NANC contractions to electrical field stimulation of guinea pig trachea are mediated by neurokinins acting primarily on NK2 receptors. Resiniferatoxin produces much more profound NANC contractile responses, which are not modified by TTX and are mediated by tachykinins acting to a large degree on NK2 receptors and, to a minor degree, on NK1 receptors.Key words: NK1 and NK2 antagonists, electrical stimulation, resiniferatoxin, guinea pig trachea.

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.

Control of neurotransmission by prostaglandins in canine trachealis smooth muscle

1984 ◽  
Vol 57 (1) ◽  
pp. 129-134 ◽  
Author(s):  
E. H. Walters ◽  
P. M. O'Byrne ◽  
L. M. Fabbri ◽  
P. D. Graf ◽  
M. J. Holtzman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Prostaglandin E2 ◽  
Electrical Field Stimulation ◽  
Tracheal Smooth Muscle ◽  
Dependent Manner ◽  
Field Stimulation ◽  
Electrical Field ◽  
Similar Time ◽  
Concentration Dependent Manner ◽  
Contractile Responses

Contractile responses of canine tracheal smooth muscle to electrical field stimulation diminished over a 2-h period of incubation. However, addition of indomethacin (10(-5) M) for a similar time not only prevented this inhibition of contractile response, but actually markedly increased the response to electrical field stimulation, suggesting that prostaglandins were responsible for the time-dependent inhibition. Measured prostaglandin E2 increased in the tissue bath over 2 h in control tissues. Addition of prostaglandin E2 to the tissue produced similar inhibition of contractile responses to electrical field stimulation in a concentration-dependent manner. In contrast, incubation alone, treatment with indomethacin, or addition of prostaglandin E2 had little, if any, effect on contractions induced by acetylcholine. We conclude that the release of prostaglandins from canine tracheal smooth muscle that occurs with time has a predominantly inhibitory effect on cholinergic neurotransmission at a prejunctional site.

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