scholarly journals Influence of Tilia tomentosa Moench Extract on Mouse Small Intestine Neuromuscular Contractility

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3505
Author(s):  
Silvia Cerantola ◽  
Sofia Faggin ◽  
Gabriela Annaloro ◽  
Federica Mainente ◽  
Raffaella Filippini ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Small Intestine ◽  
Muscle Tension ◽  
Functional Gastrointestinal Disorders ◽  
Herbal Remedies ◽  
Nitric Oxide Synthase Inhibitor ◽  
Popular Medicine ◽  
Synthase Inhibitor ◽  
Tilia Tomentosa

Functional gastrointestinal disorders (FGIDs) are characterized by abdominal pain, bloating and bowel disturbances. FGID therapy is primarily symptomatic, including treatment with herbal remedies. Flower extract of Tilia tomentosa Moench (TtM) is occasionally used as an anti-spasmodic in popular medicine. Since its effect on intestinal response is unknown, we evaluated the influence of TtM extract on small intestine contractility. Ileal preparations from C57BL/6J mice were mounted in organ baths to assess changes in muscle tension, following addition of TtM extract (0.5–36 μg/mL) or a vehicle (ethanol). Changes in contractile response to receptor- and non-receptor-mediated stimuli were assessed in ileal preparations pretreated with 12 μg/mL TtM. Alterations in the enteric nervous system neuroglial network were analyzed by confocal immunofluorescence. Increasing addition of TtM induced a marked relaxation in ileal specimens compared to the vehicle. Pretreatment with TtM affected cholinergic and tachykininergic neuromuscular contractions as well as K+-induced smooth muscle depolarization. Following incubation with TtM, a significant reduction in non-adrenergic non-cholinergic-mediated relaxation sensitive to Nω-Nitro-L-arginine methyl ester hydrochloride (pan-nitric oxide synthase inhibitor) was found. In vitro incubation of intestinal specimens with TtM did not affect the myenteric plexus neuroglial network. Our findings show that TtM-induced intestinal relaxation is mediated by nitric oxide pathways, providing a pharmacological basis for the use of TtM in FGIDs.

Abstract 18060: TRAIL Promotes Angiogenesis and Ischemia-Induced Neovascularisation via NOX4, H2O2 and Nitric Oxide-Dependent Mechanisms

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Belinda A Di Bartolo ◽  
Sian P Cartland ◽  
Leonel Prado-Lourenco ◽  
Nor Saadah M Azahri ◽  
Thuan Thai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiogenic Factor ◽  
Tubule Formation ◽  
Nitric Oxide Synthase Inhibitor ◽  
Therapeutic Implications ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
First Time

Background: Angiogenesis and neovascularization are essential processes that follow ischemia insults. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) not only induces endothelial cell (EC) death and inhibits angiogenesis, but also promotes EC migration, invasion and proliferation in vitro . These seemingly opposite effects make its role in angiogenesis in vivo unclear. Using TRAIL -/- and wild-type mice, we sought to determine the role of TRAIL in angiogenesis and neovascularisation. We also sought mechanisms in vitro . Methods and Results: Reduced vascularisation assessed by real-time in vivo 3D Vevo ultrasound imaging and CD31 staining was observed in TRAIL -/- mice 28 d after hindlimb ischemia. Moreover, reduced capillary formation and increased apoptosis was evident in TRAIL -/- muscles even at 3 d after ischemic surgery. We have previously shown that fibroblast growth factor-2 (FGF-2), a potent angiogenic factor, regulates TRAIL gene expression in vascular smooth muscle cells. Indeed, FGF-2 also regulates TRAIL expression in ECs, and FGF-2-inducible proliferation, migration and tubule formation was inhibited with siRNA targeting TRAIL. Notably, both FGF-2 and TRAIL significantly increased NOX4 expression. TRAIL-inducible angiogenic activity in ECs was inhibited with siRNAs targeting NOX4, and consistent with these, NOX4 mRNA was reduced in 3 d ischemic hindlimbs of TRAIL -/- mice. TRAIL stimulated intracellular H 2 O 2 levels in ECs, and TRAIL-inducible proliferation, migration and tubule formation was inhibited with not only PEG-catalase, a H 2 O 2 scavenger, but also blocked with L-NAME, a nitric oxide synthase inhibitor. Conclusions: This is the first demonstration showing that TRAIL promotes angiogenesis in vivo . We show for the first time that the TRAIL stimulates NOX4 expression to mediate nitric oxide-dependent angiogenic effects. This has significant therapeutic implications such that TRAIL may improve the angiogenic response to ischemia and increase perfusion recovery in patients with CVD and diabetes.

scholarly journals GABAergic Regulation of Cerebral Microvascular Tone in the Rat

1997 ◽  
Vol 17 (9) ◽  
pp. 992-1003 ◽  
Author(s):  
Andrea Fergus ◽  
Kevin S. Lee
Keyword(s):  
Nitric Oxide ◽  
Receptor Agonist ◽  
Computer Assisted ◽  
Local Concentration ◽  
Nitric Oxide Synthase Inhibitor ◽  
Cerebral Microvessels ◽  
Endogenous Gaba ◽  
Synthase Inhibitor ◽  
The Brain

The role of GABA in regulating cerebral microvessels was examined in the parenchyma of the hippocampus and the surface of the neocortex. Microvessels were monitored in in vitro slices using computer-assisted videomicroscopy, and synaptically evoked field responses were simultaneously recorded. γ-Aminobutyric acid (GABA) and the GABAA receptor agonist, muscimol, elicited vasodilation in hippocampal microvessels, whereas the GABAB receptor agonist, baclofen, elicited constriction. The muscimol-induced dilation persisted in the presence of the nitric oxide synthase inhibitor, N-nitro-l-arginine, indicating that this response is not mediated by nitric oxide. Inhibition of neuronal discharge activity with tetrodotoxin did not alter this dilation, but it fully blocked the constrictor response to baclofen. These data suggest that GABAB-mediated, but not GABAA-mediated, responses are dependent on action potential generation. The GABAA receptor antagonists, bicuculline and picrotoxin, elicited constriction, suggesting a tonic dilatory influence by endogenous GABA. Bicuculline-induced constriction was not attenuated by tetrodotoxin. In contrast, these vessels were unresponsive to the GABAB receptor antagonist, 2-hydroxysaclofen. Hippocampal microvessels dilated in response to moderate hypoxia, and this response persisted in the presence of bicuculline, indicating that the hypoxia-induced dilation is not mediated by an action at GABAA receptors. In arterioles located on the surface of the neocortex (i.e., not embedded in the parenchyma of the brain), muscimol elicited vasodilation, whereas bicuculline was ineffective. These results suggest that although these vessels are responsive to GABA, the local concentration of endogenous GABA is insufficient to elicit a tonic effect at rest. These findings raise the possibility that GABA plays a role in local neurovascular signaling in the parenchyma of the brain.

Endothelium-derived microparticles impair endothelial function in vitro

2004 ◽  
Vol 286 (5) ◽  
pp. H1910-H1915 ◽  
Author(s):  
Sergey V. Brodsky ◽  
Fan Zhang ◽  
Alberto Nasjletti ◽  
Michael S. Goligorsky
Keyword(s):  
Nitric Oxide ◽  
Surrogate Marker ◽  
Common Denominator ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Concentration Dependent Manner ◽  
Endothelial Microparticles ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor

Endothelial cell dysfunction (ECD) is emerging as the common denominator for diverse and highly prevalent cardiovascular diseases. Recently, an increased number of procoagulant circulating endothelial microparticles (EMPs) has been identified in patients with acute myocardial ischemia, preeclampsia, and diabetes, which suggests that these particles represent a surrogate marker of ECD. Our previous studies showed procoagulant potential of endothelial microparticles and mobilization of microparticles by PAI-1. The aim of this study was to test the effects of isolated EMPs on the vascular endothelium. EMPs impaired ACh-induced vasorelaxation and nitric oxide production by aortic rings obtained from Sprague-Dawley rats in a concentration-dependent manner. This effect was accompanied by increased superoxide production by aortic rings and cultured endothelial cells that were coincubated with EMPs and was inhibited by a SOD mimetic and blunted by an endothelial nitric oxide synthase inhibitor. Superoxide was also produced by isolated EMP. In addition, p22(phox) subunit of NADPH-oxidase was detected in EMP. Our data strongly suggest that circulating EMPs directly affect the endothelium and thus not only act as a marker for ECD but also aggravate preexisting ECD.

Release of glutathione from erythrocytes and other markers of oxidative stress in carbon monoxide poisoning

1997 ◽  
Vol 82 (5) ◽  
pp. 1424-1432 ◽  
Author(s):  
Stephen R. Thom ◽  
Melissa Kang ◽  
Donald Fisher ◽  
Harry Ischiropoulos
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Carbon Monoxide Poisoning ◽  
Thiobarbituric Acid ◽  
Nitric Oxide Synthase Inhibitor ◽  
Oxidized Proteins ◽  
Markers Of Oxidative Stress ◽  
Synthase Inhibitor

Thom, Stephen R., Melissa Kang, Donald Fisher, and Harry Ischiropoulos. Release of glutathione from erythrocytes and other markers of oxidative stress in carbon monoxide poisoning. J. Appl. Physiol. 82(5): 1424–1432, 1997.—Rats exposed to CO in a manner known to cause oxidative stress in brain exhibited a twofold increase in plasma levels of oxidized proteins, thiobarbituric acid-reactive substances (TBARS), oxidized glutathione (GSSG), and reduced glutathione (GSH). Changes were neither directly related to hypoxic stress from carboxyhemoglobin nor significantly influenced by circulating platelets or neutrophils. Treatment with the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester inhibited elevations in GSH and GSSG but not changes in oxidized proteins or TBARS, suggesting that two oxidative mechanisms may be operating in this model and that GSH and GSSG elevations involved nitric oxide-derived oxidants. Elevations of blood GSH and GSSG occurred at different anatomic sites, indicating that no single organ was the source of the increased peptides. Animals that underwent exchange transfusion with a hemoglobin-containing saline solution did not exhibit elevations in GSH and GSSG, suggesting that blood-borne cells released these peptides in response to oxidative stress. In in vitro studies, erythrocytes, but not platelets and leukocytes, responded to oxidative stress from peroxynitrite by releasing GSH, whereas no release was observed in response to nitric oxide or superoxide. Glucose, maltose, and cytochalasin B, agents that protect extracellular components of the hexose transport protein complex from oxidative stress, prevented GSH release. The data indicate that nitric oxide-derived oxidants are involved in CO-mediated oxidative stress within the vascular compartment and that elevations of several compounds may be useful for identifying exposures to CO likely to precipitate brain injury.

In vivo production of nitric oxide correlates with NMDA-induced cerebral hyperemia in newborn sheep

1995 ◽  
Vol 269 (1) ◽  
pp. H215-H221 ◽  
Author(s):  
F. J. Northington ◽  
J. R. Tobin ◽  
R. C. Koehler ◽  
R. J. Traystman
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Production ◽  
Nitric Oxide Synthase Inhibitor ◽  
Oxide Production ◽  
Adenosine Receptor Agonist ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Hydrogen Clearance

Stimulation of N-methyl-D-aspartate (NMDA) receptors in brain increases nitric oxide production in vitro. We tested the hypothesis that nitric oxide participates in the increase in local cerebral blood flow (CBF) caused by infusion of NMDA in anesthetized newborn sheep. We used the combined hydrogen clearance and microdialysis technique for simultaneous measurement of local CBF, infusion of drugs, and measurement of interstitial levels of L-[14C]citrulline in the parietal cortex. Release of L-[14C]citrulline into the dialysate during continuous infusion of L-[14C]arginine was used as a marker of nitric oxide production in vivo. Citrulline recovery and CBF were measured hourly during a 4-h infusion of cerebrospinal fluid containing either 1) no additional drugs, 2) 1 mM NMDA, 3) 1 mM NG-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor), 4) 1 mM NMDA + 1 mM L-NAME, 5) 0.1 mM 2-chloroadenosine (adenosine receptor agonist), or 6) 0.1 mM 2-chloroadenosine + 1 mM L-NAME. At 240 min of perfusion, CBF (ml.min-1.100 g-1; means +/- SE) was as follows: control 52 +/- 3, NMDA 116 +/- 11, L-NAME 32 +/- 5, NMDA+L-NAME 40 +/- 4,2-chloroadenosine 201 +/- 63, and 2-chloroadenosine+L-NAME 129 +/- 18. Citrulline recovery (fmol/min) at 240 min of perfusion was as follows: control 38 +/- 12, NMDA 149 +/- 21, L-NAME 9 +/- 1, NMDA+L-NAME 39 +/- 5, 2-chloroadenosine 13 +/- 5, and 2-chloroadenosine+L-NAME 17 +/- 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous nitric oxide contributes to strain-related differences in airway responsiveness in rats

1996 ◽  
Vol 80 (2) ◽  
pp. 404-410 ◽  
Author(s):  
Y. Jia ◽  
L. Xu ◽  
D. J. Turner ◽  
J. G. Martin
Keyword(s):  
Nitric Oxide ◽  
Fold Increase ◽  
Airway Responsiveness ◽  
Nitric Oxide Synthase Inhibitor ◽  
Lewis Rats ◽  
Cyclic Monophosphate ◽  
Endogenous Nitric Oxide ◽  
Fischer Rats ◽  
Synthase Inhibitor

The effects of N(omega-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, on airway responsiveness were studied in the spontaneously hyperresponsive Fischer and the control normoresponsive Lewis rat strains to investigate the role of the endogenous nitric oxide (NO) pathway in strain-related differences in airway responsiveness. Responsiveness to inhaled methacholine was significantly increased in L-NNA-treated Lewis rats but not in Fischer rats. L-NNA increased carbachol-induced tracheal contractions in vitro to a larger extent in Lewis rats compared with Fischer rats. The effect of L-NNA was abolished by removal of the epithelium. Carbachol induced a NO-dependent increase in guanosine 3′,5′-cyclic monophosphate levels in tracheal tissues but to a lesser extent in Fischer (2.1-fold increase) than in Lewis (3.7-fold increase) rats. In conclusion, endogenous NO is involved in the regulation of airway responsiveness to cholinergic agonists in rats. A relatively ineffective NO-guanosine 3′,5′-cyclic monophosphate regulatory mechanism in Fischer rats contributes, in part, to strain-related differences in airway responsiveness between Fischer and Lewis rats.

Isoflurane- and Halothane-mediated Dilation of Distal Bronchi in the Rat Depends on the Epithelium 

1997 ◽  
Vol 86 (5) ◽  
pp. 1078-1087 ◽  
Author(s):  
Kyung W. Park ◽  
Hai B. Dai ◽  
Edward Lowenstein ◽  
Olivier N. Kocher ◽  
Frank W. Sellke
Keyword(s):  
Nitric Oxide ◽  
Fourth Order ◽  
Detection System ◽  
Wistar Rat ◽  
Respiratory Epithelium ◽  
Cyclooxygenase Inhibitor ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Background Respiratory epithelium releases substance(s) that can modulate bronchoconstriction in response to constrictive agonists and enhance bronchodilation in response to certain bronchodilators. The hypothesis that the bronchodilatory effect of isoflurane and halothane depends on the epithelium was tested in rat distal bronchial segments. Methods Wistar rat bronchial segments of the fourth order (diameter approximately 100 microns) were dissected. After preconstriction with 5-hydroxytryptamine, each bronchial segment was exposed to increasing concentrations of 0% to 3% isoflurane or 0% to 3% halothane under four conditions: after epithelial rubbing, after pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine, after pretreatment with the cyclooxygenase inhibitor indomethacin, or with no preintervention (control). Changes in bronchial diameter were monitored using an in vitro video detection system. Results Both isoflurane and halothane produced concentration-dependent bronchodilation (P < 0.001 for either anesthetic; 40% +/- 11% [mean +/- SD] dilation for 3% isoflurane and 57% +/- 10% dilation for 3% halothane). For both anesthetics, bronchodilation was significantly but incompletely attenuated by epithelial rubbing (12% +/- 7% dilation for 3% isoflurane [P < 0.01] and 31% +/- 10% dilation for 3% halothane [P < 0.01]), by pretreatment with indomethacin (20% +/- 8% dilation for 3% isoflurane [P < 0.02] and 21% +/- 9% dilation for 3% halothane [P < 0.001]), or by L-NNA (9% +/- 7% dilation for 3% isoflurane [P < 0.005] and 39% +/- 12% dilation for 3% halothane [P < 0.05]). Epithelial rubbing did not impair nitroprusside-associated bronchodilation. Conclusions Isoflurane- and halothane-mediated bronchodilation depends at least partially on the epithelium and may involve both a prostanoid and nitric oxide in distal rat bronchi.

Ultrasound Improves Tissue Perfusion in Ischemic Tissue through a Nitric Oxide Dependent Mechanism

2002 ◽  
Vol 88 (11) ◽  
pp. 865-870 ◽  
Author(s):  
Valentina Suchkova ◽  
Raymond Baggs ◽  
Sanjeev Sahni ◽  
Charles Francis
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Rabbit Model ◽  
Tissue Perfusion ◽  
Nitric Oxide Synthase Inhibitor ◽  
Doppler Probe ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Dependent Mechanism

SummaryUltrasound accelerates enzymatic fibrinolysis in vitro and in animal models and may be used as an adjunct to thrombolytic therapy. Ultrasound can also affect vascular tone directly, and we have now investigated the effect of ultrasound on tissue perfusion in a rabbit model of acute muscle ischemia to characterize the magnitude and temporal course of vasodilation and determine its mechanism. After ligation of the femoral artery of rabbits, tissue perfusion in the gracilis muscle as determined using a laser Doppler probe declined by 53% from 13.7 ± 0.3 U to 6.4 ± 0.2 U. The tissue became acidotic as pH declined from normal to 7.05 ± 0.2. Application of 40 kHz ultrasound at intensities from 0.25 to 0.75 W/cm2 progressively improved perfusion over 60 min and reversed acidosis, but these effects were both completely blocked by pre-treatment with the nitric oxide synthase inhibitor LNAME. Nitric oxide synthase activity in muscle was measured using an assay based on the conversion of radiolabeled L-arginine to L-citrulline and demonstrated an increase of 3.6-fold following ultrasound exposure. This effect was greatest at locations close to the transducer and declined progressively away from it. Histologic examination showed greater capillary circumference in ultrasound exposed muscle compared to unexposed tissue with no other histologic changes. We conclude that the application of 40 kHz at low intensity improves perfusion and reverses acidosis in acutely ischemic muscle through a nitric oxide dependent mechanism.

Smooth Muscle-Derived Nitric Oxide is Elevated in Isolated Forearm Veins in Human Alcoholic Cirrhosis

1996 ◽  
Vol 91 (1) ◽  
pp. 23-28 ◽  
Author(s):  
Jeremy Ryan ◽  
Garry Jennings ◽  
Frank Dudley ◽  
Jaye Chin-Dusting
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Alcoholic Cirrhosis ◽  
Resistance Arteries ◽  
Nitric Oxide Synthase Inhibitor ◽  
Control Subjects ◽  
Synthase Inhibitor

1. Cirrhosis is often complicated by disturbances in the systemic circulation. We have previously demonstrated decreased vascular responses to vasoconstrictors in forearm resistance arteries in subjects with alcoholic cirrhosis. In the current study we investigate the role of the potent endogenous vasodilator nitric oxide in the peripheral circulation of these patients. 2. Ten patients with alcoholic cirrhosis (Pugh grade A) and 10 age-matched control subjects were studied. The effect of blockade of nitric oxide synthesis was studied both in vivo in forearm resistance arteries using forearm venous occlusion plethysmography and in vitro in veins isolated from the forearm. The role of endothelium-derived nitric oxide was studied in vivo using the endothelium-dependent vasodilator acetylcholine. 3. Mean arterial pressure and forearm basal flow in vivo were similar in the two groups. The constrictor response (percentage decrease in forearm blood flow) to noradrenaline (100 ng/min) was 26% smaller in patients with cirrhosis (31.65 ± 2.64%) than in control subjects (42.75 ± 3.87%, P = 0.037). Constrictor responses to the nitric oxide synthase inhibitor NG-monomethyl-l-arginine were not different in the two groups. Dilator responses to acetylcholine were significantly attenuated in cirrhotic patients compared with control subjects. 4. To investigate the role of smooth muscle-derived nitric oxide in vitro, all veins were stripped of their endothelium. Responses to noradrenaline were significantly diminished in veins isolated from patients with cirrhosis compared with control subjects. Incubation with the nitric oxide synthase inhibitor Nω-nitro-l-arginine had no effect on responses to noradrenaline in veins from control subjects but significantly enhanced the maximal response to noradrenaline by 23.95% (range 3.77–100%, P = 0.043) in veins from patients with cirrhosis. 5. Responses to noradrenaline were attenuated in vivo in forearm resistance arteries in patients with alcoholic cirrhosis. This impairment was also apparent in forearm isolated veins, stripped of the endothelium. Our data exclude a major role for endothelium-derived nitric oxide but highlight a possible role for smooth muscle-derived nitric oxide.

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