Optimal levels of nitric oxide are crucial for implantation in mice

1999 ◽  
Vol 11 (3) ◽  
pp. 183 ◽  
Author(s):  
H. Ota ◽  
S. Igarashi ◽  
N. Oyama ◽  
T. Tanaka ◽  
Y. Suzuki
Keyword(s):  
Nitric Oxide ◽  
Embryo Implantation ◽  
Critical Role ◽  
Mature Female ◽  
Pregnancy Rates ◽  
Nitric Oxide Donor ◽  
Control Group ◽  
Dependent Manner ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor

This study was performed to clarify the critical role of optimal levels of nitric oxide on fecun-dity in mice during the implantation period. Mature female pregnant mice were treated with either nitric oxide donor molsidomine (3, 15, 60 mg kg-1) or nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-name; 0.3, 1.5, 6 mg kg-1) every 12 h, seven times from the night of Day 2 to Day 5 of gestation. They were killed on Day 14 of gestation. Pregnancy rates in each group (n = 22) and the number of live or absorbed fetuses in each mouse was calculated. The pregnancy rates in the experimental group were reduced in a dose-dependent manner. The rate in the control group was 100%, whereas those in the 60-mg mol-sidomine and 6-mg L-name groups were 40.9 and 31.8%, respectively. Histological analysis of uteri on Day 5 of gestation after treatment with 60 mg molsidomine or 6 mg L-name suggested retarded decidualization of stromal cells or defective function of predecidualized cells. In conclusion, optimal levels of nitric oxide are crucial for endometrial function and embryo implantation.

scholarly journals Nitric Oxide–mediated Modulation of Synaptic Activity by Astrocytic P2Y Receptors

2008 ◽  
Vol 132 (3) ◽  
pp. 339-349 ◽  
Author(s):  
Bhupesh Mehta ◽  
Gulnaz Begum ◽  
Nanda B. Joshi ◽  
Preeti G. Joshi
Keyword(s):  
Nitric Oxide ◽  
P2y Receptors ◽  
Suppressive Effect ◽  
Synaptic Activity ◽  
Nitric Oxide Donor ◽  
No Production ◽  
Dependent Manner ◽  
Nitric Oxide Synthase Inhibitor ◽  
Glutamatergic Synaptic Transmission ◽  
Synthase Inhibitor

We investigated the mechanism of synaptic suppression by P2Y receptors in mixed hippocampal cultures wherein networked neurons exhibit synchronized Ca2+ oscillations (SCO) due to spontaneous glutamatergic synaptic transmission. Pharmacological studies suggested that SCO suppression was mediated by P2Y2/P2Y4 receptors. Immunostaining studies and characterization of ATP/UTP-stimulated Ca2+ responses in solitary neurons and astrocytes revealed that the SCO attenuation was effectuated by astrocytes. We demonstrate that nitric oxide released from activated astrocytes causes synaptic suppression by inhibiting neurotransmitter release. Physiological concentrations of ATP and UTP evoked NO production in astrocytes. SCO suppression was considerably diminished by removal of extracellular NO by membrane-impermeable scavenger c-PTIO or by pretreatment of cells with nitric oxide synthase inhibitor L-NAME. The nitric oxide donor DETA/NO effectively suppressed the SCO. ATP/UTP inhibited KCl-induced exocytosis at presynaptic terminals in an NO-dependent manner. In the absence of exogenously added ATP/UTP, both the NO scavenger and NOS inhibitor enhanced the frequency of SCO, implying that astrocytes release NO during spontaneous synaptic activity and exert a suppressive effect. We report for the first time that under physiological conditions astrocytes use NO as a messenger molecule to modulate the synaptic strength in the networked neurons.

Dipyridamole Potentiates the Endothelium-Dependent and -Independent Vasomotion in Isolated Human Small Arteries

1996 ◽  
Vol 1 (3) ◽  
pp. 203-209 ◽  
Author(s):  
Roberto Pedrinelli
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Adenosine Receptor ◽  
Guanosine Monophosphate ◽  
Muscarinic Agonist ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adenosine Receptor Agonist ◽  
Synthase Inhibitor

Background To investigate the effects of dipyridamole, a drug with phosphodiesterase-, adenosine reuptake-inhibiting, and prostacyclin-stimulating activity on the biological actions of nitric oxide, 30 norepinephrine-precontracted subcutaneous arterioles were prepared from specimens removed during surgery. Methods and Results Specimens were mounted on a myograph and relaxed through either acetylcholine, a muscarinic agonist that stimulates endothelial nitric oxide production, or sodium nitroprusside, an endothelium-independent vasodilator. Studies were performed under control conditions and after dipyridamole which potentiated in a concentration-dependent manner the vasorelaxation induced both by acetylcholine and sodium nitroprusside, indicating an endothelium-independent mechanism of action. The contribution of nitric oxide to the relaxation produced by acetylcholine was confirmed by N-monomethyl-L-arginine, a nitric oxide synthase inhibitor. In contrast, indomethacin, a cyclo-oxygenase inhibitor, was ineffective, indicating that prostacyclin stimulation could not explain the effect of dipyridamole. CGS 21680 C, an A2-selective adenosine receptor agonist insensitive to tissue deaminase, did not influence the relaxations induced by acetylcholine, suggesting that interference with adenosine metabolism was not implicated in the potentiating action of dipyridamole. Conclusion Dipyridamole potentiated the vasorelaxing effect of acetylcholine and sodium nitroprusside in human subcutaneous arterioles; neither prostacyclin stimulation nor A2 adenosine receptor stimulation could explain this effect. The data are consistent with an increase in intracellular cyclic 3’ 5'-guanosine monophosphate levels secondary to the phosphodiesterase-inhibiting properties of the drug.

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.

Inhibition of nitric oxide synthases prevents and reverses α,β-meATP-induced neck muscle nociception in mice

Cephalalgia ◽  
2010 ◽  
Vol 30 (10) ◽  
pp. 1225-1232 ◽  
Author(s):  
Jens Ellrich ◽  
Andreas Fischer ◽  
Joachim M Gilsbach ◽  
Anna Makowska ◽  
Peter Spangenberg
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Nitric Oxide Synthases ◽  
Neck Muscles ◽  
Neck Muscle ◽  
Dependent Manner ◽  
Nitric Oxide Synthase Inhibitor ◽  
Therapeutic Concepts ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Introduction: Tension-type headache (TTH) is associated with noxious input from neck muscles. Intravenous administration of the unspecific nitric oxide synthase inhibitor L-NMMA in chronic TTH patients caused analgesia and reduction of neck muscle tenderness. Methods: The unspecific nitric oxide synthase inhibitor L-NMMA was applied in an experimental model for neck muscle nociception in anesthetized mice ( N = 25). Results: Local injection of α,β-meATP into semispinal neck muscles induced sustained facilitation of brainstem nociception as monitored by the jaw-opening reflex. Preceding intraperitoneal administration of L-NMMA (0.05, 0.1, 1 mg/kg) prevented reflex facilitation evoked by α,β-meATP in a dose-dependent manner. Intraperitoneal injection of L-NMMA subsequent to intramuscular α,β-meATP application reversed established brainstem reflex facilitation back to baseline values. Discussion: Both experiments with preceding and subsequent L-NMMA indicate the involvement of nitric oxide synthases in the induction and maintenance of facilitation. However, future experiments will have to address the involvement of various isoenzymes in order to provide for new therapeutic concepts in TTH.

scholarly journals Effect of cross-linked hemoglobin transfusion on endothelial-dependent dilation in cat pial arterioles

1998 ◽  
Vol 275 (4) ◽  
pp. H1313-H1321 ◽  
Author(s):  
Yoshio Asano ◽  
Raymond C. Koehler ◽  
John A. Ulatowski ◽  
Richard J. Traystman ◽  
Enrico Bucci
Keyword(s):  
Nitric Oxide ◽  
Hemoglobin Concentration ◽  
Nitric Oxide Donor ◽  
Nitric Oxide Synthase Inhibitor ◽  
Cranial Window ◽  
Dilatory Response ◽  
Pial Arterioles ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Arteriolar Diameter

We determined whether addition of hemoglobin to the plasma would inhibit endothelial-dependent dilation in brain where tight endothelial junctions limit hemoglobin extravasation. Pial arteriolar diameter was measured by intravital microscopy through closed cranial windows in anesthetized cats either without transfusion (hematocrit = 32%) or after exchange transfusion with an albumin or sebacyl-cross-linked human hemoglobin solution (hematocrit = 18%). Dilation of small, medium, and large arterioles to acetylcholine and ADP was not significantly altered by hemoglobin transfusion. The dilatory responses were inhibited by the nitric oxide synthase inhibitor N G-nitro-l-arginine, although significant dilation to 30 μM acetylcholine persisted in small arterioles in the control and albumin-transfused group but not in the hemoglobin-transfused group. The dilatory response to the nitric oxide donor 3-morpholinosydnonimine was unaffected by albumin or hemoglobin transfusion, but the response to nitroprusside was reduced by one-third after hemoglobin transfusion. When cross-linked hemoglobin was superfused through the cranial window, the acetylcholine response became inhibited at a hemoglobin concentration of 0.1 μM and was completely blocked at 10 μM. Because this concentration is substantially less than the 500 μM hemoglobin concentration in plasma after transfusion when there was no inhibition of the acetylcholine response, hemoglobin permeation of the blood-brain barrier was considered negligible. We conclude that exchange of red cell-based hemoglobin with plasma-based hemoglobin does not produce a more effective sink for endothelial-derived nitric oxide evoked by agonist receptor-mediated activation. Furthermore, decreased hematocrit does not affect agonist-evoked endothelial-dependent dilation.

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