scholarly journals Enteric descending and afferent neural signaling stimulated by giant migrating contractions: essential contributing factors to visceral pain

2007 ◽  
Vol 292 (2) ◽  
pp. G572-G581 ◽  
Author(s):  
Sushil K. Sarna
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Nitric Oxide Synthase ◽  
Muscarinic Receptors ◽  
Visceral Pain ◽  
Intestinal Segment ◽  
Descending Inhibition ◽  
Oxide Synthase ◽  
Stimulation Of ◽  
Giant Migrating Contractions

We investigated whether strong compression of an intestinal segment by giant migrating contractions (GMCs) initiates pseudoaffective signals from the gut, similar to those initiated by its distension with a balloon. The experiments were performed on conscious dogs by using close intra-arterial infusions of test substances that affect the receptors only in the infused segment. The stimulation of GMCs by close intra-arterial infusion of CGRP or distension of an intestinal segment by balloon increased the heart rate; the increase in heart rate was greater when the balloon distension and GMCs occurred concurrently in separate intestinal segments. The suppression of contractility in the distended segment blocked the increase in heart rate. By contrast, the stimulation of rhythmic phasic contractions (RPCs) or their spontaneous occurrence did not increase the heart rate. The occurrence of GMCs as well as intestinal distension also produced descending inhibition. The descending inhibition was blocked by the inhibition of nitric oxide synthase, but it was unaffected by the inhibition of adenylyl cyclase, purinergic receptors P2X and P2Y, and muscarinic receptors M1 and M2. The synaptic transmission for descending inhibition was mediated primarily by nicotinic receptors and activation of nitric oxide synthase. It was unaffected by the inhibition of tachykinin receptors NK1, NK2, and NK3; serotonin receptors 5-HT1A, 5-HT2/5-HT1C, 5-HT3, and 5-HT4; and muscarinic receptors. Our findings show that GMCs, but not RPCs, initiate pseudoaffective signals from the gut. In the presence of visceral hypersensitivity or impaired descending inhibition, the GMCs may become a noxious stimulus.

scholarly journals Optogenetic Stimulation Reduces Neuronal Nitric Oxide Synthase Expression After Stroke

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Arjun Vivek Pendharkar ◽  
Daniel L Smerin ◽  
Lorenzo Gonzales ◽  
Eric Wang ◽  
Sabrina L Levy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Neuronal Nitric Oxide Synthase ◽  
Optogenetic Stimulation ◽  
Oxide Synthase ◽  
Nnos Expression ◽  
Stimulation Of ◽  
Nnos Inhibition

Abstract INTRODUCTION Poststroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of neurovascular response in acute stroke but its role in subacute recovery remains unclear. Here we investigate nNOS expression in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examine the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. METHODS Transgenic Thy1-ChR2-YFP male mice (10-12 wk) were used. Stereotaxic surgery was performed to implant a fiber cannula in the cLCN and animals underwent intraluminal middle cerebral artery suture occlusion (30 min). Optogenetic stimulation began at poststroke (PD) day 5 and continued until PD14. Sensorimotor tests were used to assess behavioral recovery at PD4, 7, 10, and 14. At PD15, primary motor cortex from both ipsi- and contralesional motor cortex (iM1, cM1) were dissected. nNOS mRNA and protein levels were examined using quantitative polymerase chain reaction and western blot. In another set of studies, nNOS inhibitor ARL 17477 dihydrochloride (10 mg/kg, intraperitoneally) was administered daily between PD5-14 and functional recovery was evaluated using sensorimotor tests. RESULTS cLCN stimulated stroke mice demonstrated significant improvement in speed (cm/s) on the rotating beam task at PD10 and 14 day (P < .05, P < .001 respectively). nNOS mRNA and protein expression was significantly and selectively decreased in cM1 of cLCN stimulated mice (P < .05). The reduced nNOS expression in cM1 was negatively correlated with improved recovery (R2 = −0.839, Pearson P = .009). nNOS inhibitor-treated stroke mice exhibited a significant functional improvement in speed at PD10, when compared to stroke mice receiving vehicle (saline) (P < .05). CONCLUSION Our results suggest that nNOS may play a maladaptive role in poststroke recovery. Optogenetic stimulation of cLCN and systemic nNOS inhibition produce functional benefits after stroke.

Stimulation of the endogenous hydrogen sulfide synthesis suppresses oxidative–nitrosative stress and restores endothelial-dependent vasorelaxation in old rats

2020 ◽  
Vol 98 (5) ◽  
pp. 275-281 ◽  
Author(s):  
L.A. Mys ◽  
N.A. Strutynska ◽  
Y.V. Goshovska ◽  
V.F. Sagach
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Nitric Oxide Synthase ◽  
Vascular Reactivity ◽  
Nitrosative Stress ◽  
Rat Aorta ◽  
Aortic Tissue ◽  
Old Rats ◽  
Oxide Synthase ◽  
Stimulation Of

Hydrogen sulfide (H2S) is an endogenous gas transmitter with profound effects on the cardiovascular system. We hypothesized that stimulation of H2S synthesis might alleviate age-associated changes in vascular reactivity. Pyridoxal-5-phosphate (PLP), the coenzyme of H2S-synthesizing enzymes, was administrated to old male Wistar rats per os at a dose of 0.7 mg/kg body mass once a day for 2 weeks. H2S content in the aortic tissue, markers of oxidative stress, inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS), arginase activities, and endothelium-dependent vasorelaxation of the aortic rings were studied. Our results showed that PLP restored endogenous H2S and low molecular weight S-nitrosothiol levels in old rat aorta to the levels detected in adults. PLP significantly reduced diene conjugate content, hydrogen peroxide and peroxynitrite generation rates, and iNOS and arginase activity in the aortic tissue of old rats. PLP also greatly improved acetylcholine-induced relaxation of old rat aorta (47.7% ± 4.8% versus 18.4% ± 4.1% in old rats, P < 0.05) that was abolished by NO inhibition with N-nitro-l-arginine methyl ester hydrochloride (L-NAME) or H2S inhibition with O-carboxymethylhydroxylamine (O-CMH). Thus, PLP might be used for stimulation of endogenous H2S synthesis and correction of oxidative and nitrosative stress and vessel tone dysfunction in aging and age-associated diseases.

scholarly journals Nitric oxide produced by periostial hemocytes modulates the bacterial infection-induced reduction of the mosquito heart rate

2020 ◽  
Vol 223 (15) ◽  
pp. jeb225821
Author(s):  
Tania Y. Estévez-Lao ◽  
Leah T. Sigle ◽  
Scherly N. Gomez ◽  
Julián F. Hillyer
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Nitric Oxide Synthase ◽  
Bacterial Infection ◽  
Micrococcus Luteus ◽  
Cardiac Phenotype ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Neuropeptide F ◽  
Oxide Synthase

ABSTRACTThe circulatory and immune systems of mosquitoes are functionally integrated. An infection induces the migration of hemocytes to the dorsal vessel, and specifically, to the regions surrounding the ostia of the heart. These periostial hemocytes phagocytose pathogens in the areas of the hemocoel that experience the highest hemolymph flow. Here, we investigated whether a bacterial infection affects cardiac rhythmicity in the African malaria mosquito, Anopheles gambiae. We discovered that infection with Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis, but not Micrococcus luteus, reduces the mosquito heart rate and alters the proportional directionality of heart contractions. Infection does not alter the expression of genes encoding crustacean cardioactive peptide (CCAP), FMRFamide, corazonin, neuropeptide F or short neuropeptide F, indicating that they do not drive the cardiac phenotype. Infection upregulates the transcription of two superoxide dismutase (SOD) genes, catalase and a glutathione peroxidase, but dramatically induces upregulation of nitric oxide synthase (NOS) in both the heart and hemocytes. Within the heart, nitric oxide synthase is produced by periostial hemocytes, and chemically inhibiting the production of nitric oxide using l-NAME reverses the infection-induced cardiac phenotype. Finally, infection induces the upregulation of two lysozyme genes in the heart and other tissues, and treating mosquitoes with lysozyme reduces the heart rate in a manner reminiscent of the infection phenotype. These data demonstrate an exciting new facet of the integration between the immune and circulatory systems of insects, whereby a hemocyte-produced factor with immune activity, namely nitric oxide, modulates heart physiology.

scholarly journals Contrasting effects of N5-substituted tetrahydrobiopterin derivatives on phenylalanine hydroxylase, dihydropteridine reductase and nitric oxide synthase

2000 ◽  
Vol 348 (3) ◽  
pp. 579-583 ◽  
Author(s):  
Ernst R. WERNER ◽  
Hans-Jörg HABISCH ◽  
Antonius C. F. GORREN ◽  
Kurt SCHMIDT ◽  
Laura CANEVARI ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Phenylalanine Hydroxylase ◽  
Neuronal Nitric Oxide Synthase ◽  
Dihydropteridine Reductase ◽  
Redox Active ◽  
Competitive Inhibitors ◽  
Oxide Synthase ◽  
Active Contribution ◽  
Stimulation Of

Tetrahydrobiopterin [(6R)-5,6,7,8-tetrahydro-L-biopterin, H4biopterin] is one of several cofactors of nitric oxide synthases (EC 1.14.13.39). Here we compared the action of N5-substituted derivatives on recombinant rat neuronal nitric oxide synthase with their effects on dihydropteridine reductase (EC 1.6.99.7) and phenylalanine hydroxylase (EC 1.14.16.1), the well-studied classical H4biopterin-dependent reactions. H4biopterin substituted at N5 with methyl, hydroxymethyl, formyl and acetyl groups were used. Substitution at N5 occurs at a position critical to the redox cycle of the cofactor in phenylalanine hydroxylase/dihydropteridine reductase. We also included N2ʹ-methyl H4biopterin, a derivative substituted at a position not directly involved in redox cycling, as a control. As compared with N5-methyl H4biopterin, N5-formyl H4biopterin bound with twice the capacity but stimulated nitric oxide synthase to a lesser extent. Depending on the substituent used, N5-substituted derivatives were redox-active: N5-methyl- and N5-hydroxylmethyl H4biopterin, but not N5-formyl- and N5-acetyl H4biopterin, reduced 2,6-dichlorophenol indophenol. N5-Substituted H4biopterin derivatives were not oxidized to products serving as substrates for dihydropteridine reductase and, depending on the substituent, were competitive inhibitors of phenylalanine hydroxylase: N5-methyl- and N5-hydroxymethyl H4biopterin inhibited phenylalanine hydroxylase, whereas N5-formyl- and N5-acetyl H4biopterin had no effect. Our data demonstrate differences in the mechanism of stimulation of phenylalanine hydroxylase and nitric oxide synthase by H4biopterin. They are compatible with a novel, non-classical, redox-active contribution of H4biopterin to the catalysis of the nitric oxide synthase reaction.

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