Nitric oxide mediates human chorionic gonadotrophin-induced prostaglandin E generation in rat oocyte - cumulus complexes

1997 ◽  
Vol 9 (4) ◽  
pp. 391 ◽  
Author(s):  
Alicia Jawerbaum ◽  
Elida T. Gonzalez ◽  
Alicia Faletti ◽  
Virginia Novaro ◽  
Martha A. F. Gimeno
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
No Synthase ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Prostaglandin E ◽  
No Donors ◽  
Nos Inhibitors ◽  
Preovulatory Follicles

To determine whether nitric oxide (NO) generation mediates human chorionic gonadotrophin (hCG)-induced prostaglandin E (PGE) secretion by oocyte–cumulus complexes (OCC), the secretion of PGE by cultured rat OCC in the presence of NO donors and NO synthase (NOS) inhibitors was characterized. NO donors (sodium nitroprusside and 3-morpholino-sydnonimine- hydrochloride) increased PGE accumulation in OCC to values similar to those obtained in the presence of hCG. The three NOS inhibitors tested (N G -nitro-L-arginine methyl ester, NG -monomethyl-L-arginine and aminoguanidine) prevented the hCG-induced PGE accumulation in cultured OCC. This effect appears to be specific since D-enantiomers NG -nitro-D-arginine methyl ester and NG -monomethyl-D-arginine had no effect. The present results suggest that NO mediates the hCG-induced accumulation of PGE in rat OCC, a process which may occur in vivo in preovulatory follicles prior to ovulation.

Effects of NG-substituted arginines on coronary vascular function after endotoxin

1993 ◽  
Vol 75 (1) ◽  
pp. 424-431 ◽  
Author(s):  
M. J. Winn ◽  
B. Vallet ◽  
N. K. Asante ◽  
S. E. Curtis ◽  
S. M. Cain
Keyword(s):  
Nitric Oxide ◽  
Vascular Function ◽  
Endotoxic Shock ◽  
No Synthase ◽  
Relaxing Factor ◽  
Nos Inhibitors ◽  
Nos Inhibitor ◽  
Endothelium Derived Relaxing Factor ◽  
Constrictor Response

We investigated the responses of canine coronary rings to endothelium-derived relaxing factor-nitric oxide- (EDRF-NO) dependent agonists and NO synthase (NOS) inhibitors 3 h after endotoxic shock was induced in dogs by lipopolysaccharide infusion (LPS; 2 mg/kg). EDRF-NO-dependent relaxation to thrombin [control maximum response produced after administration of thrombin (Emax) was -85.2 +/- 7.0% of the constrictor response produced by the thromboxane analogue U-46619], acetylcholine (control Emax -88.4 +/- 3.4%), or bradykinin (control Emax -80.5 +/- 2.2%) was not inhibited by LPS (Emax thrombin -75.9 +/- 9.5%; Emax acetylcholine -90.2 +/- 2.4%; Emax bradykinin -91.6 +/- 3.4%). The NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) (10(-6)-3 x 10(-4) M) caused constriction of rings with endothelium (Emax 36.3 +/- 5.6%), an effect that was greater after LPS (Emax 59.2 +/- 4.1%; P < 0.05). D-NMMA had no effect in control, but it increased tension after LPS (Emax 20.8 +/- 9.7%). Contrary to expectations, L- and D-NMMA relaxed endothelium-denuded rings (-30.4 +/- 8.7% L-NMMA; -45.1 +/- 11.7% D-NMMA; P < 0.05). However, neither agent caused relaxation after in vivo LPS (10.2 +/- 3.4% L-NMMA; 8.9 +/- 5.2% D-NMMA). N omega-nitro-L-arginine-methylester (L-NAME) and nitro-L-arginine (10(-6)-3 x 10(-4) M) increased tension (Emax 82.3 +/- 23.9 and 73.1 +/- 8.8%, respectively) but only when endothelium was present, and the increases were no greater in LPS-treated groups than in controls (with LPS: Emax L-NAME 87.3 +/- 16.5%; Emax nitro-L-arginine 65.7 +/- 3.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

5-HT-induced colonic contractions: enteric locus of action and receptor subtypes

1997 ◽  
Vol 273 (1) ◽  
pp. G68-G74 ◽  
Author(s):  
S. Graf ◽  
S. K. Sarna
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Contractile Response ◽  
No Synthase ◽  
Enteric Neurons ◽  
Receptor Subtypes ◽  
Arterial Infusion ◽  
Stimulation Of

The role of 5-hydroxytryptamine (5-HT), its enteric locus of action, and the receptor subtypes involved in the stimulation of in vivo phasic contractions in the colon were investigated by close intra-arterial infusions in conscious dogs. The contractile response to 5-HT was blocked completely by prior close intra-arterial infusion of atropine and reduced significantly by prior close intra-arterial infusions of tetrodotoxin and hexamethonium. The contractile response was, however, enhanced by the inhibition of nitric oxide (NO) synthase by a prior close intra-arterial infusion of N omega-nitro-L-arginine methyl ester. Prior close intra-arterial infusions of 5-HT1A/5-HT1B, 5-HT2A, 5-HT2C, and 5-HT4 receptor antagonists had no significant effect on the contractile response to 5-HT. By contrast, 5-HT3 receptor antagonist significantly and dose dependently inhibited the contractile response to 5-HT. We conclude that the in vivo phasic contractile response to 5-HT in the colon is mediated mainly by 5-HT3 receptors located on pre- and postsynaptic cholinergic enteric neurons. 5-HT receptors may also be localized on nonadrenergic, noncholinergic inhibitory motoneurons that use NO as a neurotransmitter.

Effect of in vivo nitrate tolerance on hypersensitivity to NO donors after NO-synthase blockade

2002 ◽  
Vol 80 (11) ◽  
pp. 1106-1118 ◽  
Author(s):  
Jodan D Ratz ◽  
Michael A Adams ◽  
Brian M Bennett
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Nitrate Tolerance ◽  
Metabolite Formation ◽  
No Donor ◽  
No Donors ◽  
Nos Inhibitors ◽  
Pressure Lowering ◽  
Oxide Synthase

Animals treated with nitric oxide synthase (NOS) inhibitors exhibit marked hypersensitivity to the blood pressure lowering effects of exogenous nitric oxide (NO) donors. We used this model as a sensitive index to evaluate the relative importance of reduced biotransformation of glyceryl trinitrate (GTN) to NO in the development of nitrate tolerance. NOS-blockade hypertension using NG-nitro-L-arginine methyl ester (L-NAME) caused a marked enhancement of the mean arterial pressure (MAP) decrease mediated by GTN in nontolerant rats. However, even large doses of GTN were unable to change the MAP in GTN-tolerant, NOS-blockade hypertensive animals. In contrast, the MAP responses to the spontaneous NO donor sodium nitroprusside (SNP) were completely unaltered in either tolerant rats or tolerant NOS-blockade hypertensive animals, indicating that NO-dependent vasodilatory mechanisms remain intact despite the development of GTN tolerance. The MAP-lowering effects of GTN in NOS-blockade hypertensive animals were restored 48 h after cessation of chronic GTN exposure. These alterations in the pharmacodynamic response to GTN during tolerance development and reversal were associated with parallel changes in the pattern of GTN metabolite formation, suggesting that the activity of one or more enzymes involved in nitrate metabolism was altered as a consequence of chronic GTN exposure. These findings suggest that the vasodilation resulting from the vascular biotransformation of GTN to NO (or a closely related species) is severely compromised in nitrate-tolerant animals, and that although other mechanisms may contribute to the vascular changes observed following the development of GTN tolerance, decreased GTN bioactivation is likely the most important.Key words: biotransformation, glyceryl trinitrate, hypertension, nitric oxide, tolerance.

scholarly journals Progesterone production in bovine luteal cells treated with drugs that modulate nitric oxide production

Reproduction ◽  
2003 ◽  
pp. 389-395 ◽  
Author(s):  
JJ Jaroszewski ◽  
M Bogacki ◽  
DJ Skarzynski
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Sodium Nitroprusside ◽  
Nitrate Concentration ◽  
No Synthase ◽  
Dependent Manner ◽  
No Donors ◽  
Luteal Cells ◽  
Progesterone Production ◽  
Cells Cultured

The aim of this study was to investigate the influence of nitric oxide (NO) donors (S-nitroso-L-acetyl penicillamine, spermine-NO complex and sodium nitroprusside) and NO synthase inhibitors (N(omega)-nitro-L-arginine methyl ester, N(omega)-nitro-l-arginine, and (+/-)-2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine) on progesterone production by dispersed bovine luteal cells cultured for 24 h. All NO donors inhibited progesterone production and increased nitrite or nitrate concentration in the medium in a dose-dependent manner. Secretion of progesterone was reduced to 75% (P < 0.01), 56% (P < 0.001) and 37% (P < 0.001) by S-nitroso-L-acetyl penicillamine; to 65% (P < 0.001), 45% (P < 0.001) and 33% (P < 0.001) by spermine-NO complex and to 77% (P < 0.05), 74% (P < 0.01) and 54% (P < 0.001) by sodium nitroprusside treatments at concentrations of 10(-5), 10(-4) and 10(-3) mol l(-1), respectively, compared with the concentration of this hormone measured in cells cultured in medium alone. NO synthase inhibitors decreased significantly (P < 0.05) nitrite or nitrate concentration and increased progesterone secretion with different potency at different doses. Significant increases in progesterone production were observed after N(omega)-nitro-L-arginine methyl ester treatment at a concentration of 10(-5) mol l(-1) and 10(-4) mol l(-1), and after N(omega)-nitro-l-arginine administration at a concentration of 10(-6) mol l(-1) (P < 0.01) and 10(-5) mol l(-1) (P < 0.05), compared with the concentration of this hormone measured in control cells. The results indicate that both NO donors and NO synthase inhibitors regulate steroidogenesis in cultured bovine luteal cells from days 10 to 14 of the oestrous cycle; however, the degree of progesterone inhibition by NO donors and stimulation by NO synthase inhibitors was dependent on the drug used.

Role of tyrosine phosphorylation in the regulation of cerebral vascular tone in newborn pig in vivo

1999 ◽  
Vol 276 (1) ◽  
pp. H185-H193 ◽  
Author(s):  
Helena Parfenova ◽  
Alex Fedinec ◽  
Charles W. Leffler
Keyword(s):  
Arachidonic Acid ◽  
Methyl Ester ◽  
Tyrosine Phosphorylation ◽  
Cerebral Circulation ◽  
No Synthase ◽  
Prostaglandin E ◽  
Phenylarsine Oxide ◽  
Newborn Pigs

The role of tyrosine phosphorylation was investigated using protein tyrosine phosphatase inhibitors in newborn pigs equipped with a cranial window in vivo. We tested the hypothesis that cyclooxygenase and nitric oxide (NO) synthase are physiological targets for tyrosine phosphorylation in cerebral circulation. Phenylarsine oxide dilated pial arterioles and increased prostacyclin and prostaglandin E2 in cortical periarachnoid fluid; these responses were inhibited by indomethacin. N ω-nitro-l-arginine methyl ester (l-NAME) and N ω-nitro-l-arginine (l-NNA) inhibited the vasodilation to phenylarsine oxide; the effects of NO synthase inhibitors and indomethacin were additive. Cyclooxygenase-mediated vascular responses were assessed using topical application of arachidonic acid. Phenylarsine oxide and sodium orthovanadata potentiated vasodilation and prostanoid synthesis in response to arachidonic acid. N ω-nitro-l-arginine methyl ester and N ω-nitrol-arginine did not affect vasodilation or prostanoid production in response to arachidonic acid, indicating no cross talk between cyclooxygenase and NO synthase. These data indicate that cyclooxygenase and NO synthase are physiological targets for tyrosine phosphorylation in the cerebral circulation of newborn pigs.

Nitric oxide mediates increased prostaglandin E production by oocyte - cumulus complexes in the non-insulin-dependent diabetic rat

1998 ◽  
Vol 10 (2) ◽  
pp. 185 ◽  
Author(s):  
Alicia Jawerbaum ◽  
Elida T. Gonzalez ◽  
Virginia Novaro ◽  
Alicia Faletti ◽  
Martha A. F. Gimeno
Keyword(s):  
Nitric Oxide ◽  
Diabetic Rats ◽  
No Synthase ◽  
Diabetic Rat ◽  
Prostaglandin E ◽  
Basal Secretion ◽  
No Donors ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic ◽  
Synthase Inhibitor

Previous work described an increase in prostaglandin E (PGE) production by oocyte–cumulus complexes (OVA) obtained from non-insulin-dependent diabetic rats. More recently, it has been found that in control OVA nitric oxide (NO) mediates hCG-induced PGE secretion. To determine whether increases in PGE secretion by diabetic OVA are mediated by NO, the present study has evaluated the secretion of PGE by diabetic OVA, cultured in the absence or presence of hCG, NO donors (sodium nitroprusside (NP) and 3-morpholino-sydnonimine-hydrochloride (SIN–1)), and a NO synthase inhibitor (NG monomethyl-L-arginine; L-NMMA). hCG, NP and SIN–1 increased PGE secretion by diabetic OVA. L-NMMA did not modify basal secretion of PGE by control OVA but lowered PGE production in diabetic OVA to control values. L-NMMA prevented the hCG-induced PGE accumulation in control and diabetic OVA, and the quantities of PGE produced were similar to those of control OVA but lower than in diabetic OVA incubated in the absence of hCG. The effect of L-NMMA seems to be specific since NG monomethyl-D-arginine had no effect. NO synthase activity was higher in diabetic ovaries than in controls. The present results suggest that NO mediates the increased PGE production by diabetic OVA, probably a result of overproduction of NO.

Abstract 1286: Neuronal Nitric Oxide Synthase Regulates Basal Vascular Tone in the Healthy Human Forearm in vivo.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Mike Seddon ◽  
Phil Chowienczyk ◽  
Barbara Casadei ◽  
Ajay Shah
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Vascular Tone ◽  
Venous Occlusion ◽  
No Synthase ◽  
Healthy Human ◽  
Vasodilator Response ◽  
Nos Inhibitors ◽  
Human Forearm

Nitric oxide (NO) has an established role in the maintenance of vascular tone, generally assumed to be mediated by endothelial NO synthase (eNOS). Previous studies using the non-selective NOS inhibitor N G monomethyl-L-arginine (L-NMMA) in humans confirmed the in vivo importance of NO but the contribution of neuronal NO synthase (nNOS) is unknown due to the lack of available selective NOS inhibitors for human use. In this study, we investigated for the first time in humans the effects of S-methyl-L-thiocitrulline (SMTC), a competitive nNOS-selective inhibitor with 17-fold selectivity over eNOS. SMTC or L-NMMA were infused into the brachial artery of healthy male volunteers and forearm blood flow was measured by venous occlusion plethysmography. SMTC 0.025, 0.05, 0.1 and 0.2 μmol/min caused a dose-dependent reduction in basal blood flow in the infused arm of 9.2±1.9, 16.2±2.9, 22.9±3.9 and 30.1±3.8% respectively (n=10; mean±SE; all P<0.01). Substantially higher doses of L-NMMA of 0.5, 1, 2 and 4 μmol/min were required to reduce basal flow by 11.5±3.0, 25.1±3.0, 33.7±3.0 and 37.4±3.1% respectively (n=10). The highest dose of SMTC (ie, 0.2 μmol/min) tested had no significant effect on the vasodilator response to acetylcholine (ACh): Ach 40 and 80nmol/min increased blood flow by 3.93±0.64 and 5.54±0.69 ml/min/100mls tissue above baseline during saline co-infusion versus 3.95±0.69 and 4.90±0.71 ml/min/100mls tissue during SMTC co-infusion (n=10; P=NS). In contrast, L-NMMA significantly reduced the response to these doses of ACh by 64±9.9 and 60±10% (n=10; both P<0.01). The effect of SMTC on basal blood flow was completely abolished in the presence of the NOS substrate L-arginine (n=6; P<0.001) but was unaffected by the stereoisomer D-arginine (n=6). SMTC had no effect on the vasodilator response to sodium nitroprusside (n=5). In conclusion , SMTC reduced basal blood flow by stereospecific inhibition of the L-arginine:NO pathway but did not affect the eNOS-mediated vasodilator response to ACh. These results indicate that nNOS has a crucial role in the regulation of basal vascular tone in the human forearm in vivo .

Inhibition of nitric oxide synthase attenuates NNMU-induced alveolar injury in vivo

1997 ◽  
Vol 273 (6) ◽  
pp. L1167-L1173 ◽  
Author(s):  
Wilhelm S. Cruz ◽  
Michael A. Moxley ◽  
John A. Corbett ◽  
William J. Longmore
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Methyl Ester ◽  
Lung Injury ◽  
Protein Ratio ◽  
Nos Inhibitors ◽  
Elevated Expression ◽  
Nos Inhibitor ◽  
Oxide Synthase

The purpose of this study was to determine if the acute alveolar injury induced by subcutaneous injections of N-nitroso- N-methylurethane (NNMU) in rats is mediated by nitric oxide (NO ⋅). We show that intraperitoneal injections of the NO ⋅ synthase (NOS) inhibitor N ω-nitro-l-arginine methyl ester (l-NAME) or aminoguanidine significantly attenuate the NNMU-induced alveolar injury as assessed by 1) normalization of the alveolar-arterial O2difference, 2) attenuation of the lowered phospholipid-to-protein ratio in the crude surfactant pellet (CSP), 3) attenuation of the elevated minimal surface tension of the CSP, and 4) attenuation of polymorphonuclear neutrophilic infiltration into the alveolar space. Injections of N ω-nitro-d-arginine methyl ester, the inactive stereoisoform ofl-NAME, did not affect the acute lung injury. Western blot analysis of whole lung homogenates demonstrate an elevated expression of transcriptionally inducible, Ca2+-independent NOS (iNOS) in NNMU-injected rats compared with control saline-injected rats. NOS inhibitors did not affect NNMU-induced iNOS expression. These investigations demonstrate that the inhibition of NOS attenuates NNMU-induced acute lung injury, suggesting a role for NO ⋅ in the progression of acute respiratory distress syndrome.

Differential effects of l-NAME on rat venular hydraulic conductivity

2000 ◽  
Vol 279 (4) ◽  
pp. H2017-H2023 ◽  
Author(s):  
Rolando E. Rumbaut ◽  
Jianjie Wang ◽  
Virginia H. Huxley
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Methyl Ester ◽  
Hydraulic Conductivity ◽  
No Synthase ◽  
Vascular Effects ◽  
Nos Inhibitors ◽  
Before And After ◽  
Nos Inhibitor

The role of nitric oxide (NO) in microvascular permeability remains unclear because both increases and decreases in permeability by NO synthase (NOS) inhibitors have been reported. We sought to determine whether blood-borne constituents modify venular permeability responses to the NOS inhibitor N G-nitro-l-arginine methyl ester (l-NAME). We assessed hydraulic conductivity ( L p) of pipette-perfused rat mesenteric venules before and after exposure to 10−4 M l-NAME. In the absence of blood-borne constituents, l-NAME reduced L p by nearly 50% (from a median of 2.4 × 10−7cm · s−1 · cmH2O−1, n = 17, P < 0.001). The reduction in L p by l-NAME was inhibited by a 10-fold molar excess of l-arginine but notd-arginine ( n = 6). In a separate group of venules, blood flow was allowed to resume during exposure tol-NAME. In vessels perfused by blood duringl-NAME exposure, L p increased by 78% (from 1.4 × 10−7cm · s−1 · cmH2O−1, n = 10, P < 0.01). N G-nitro-d-arginine methyl ester did not affect L p in either of the two groups. These data imply that NO has direct vascular effects on permeability that are opposed by secondary changes in permeability mediated by blood-borne constituents.

Nitric oxide and cerebral blood flow responses to hyperbaric oxygen

2000 ◽  
Vol 88 (4) ◽  
pp. 1381-1389 ◽  
Author(s):  
Ivan T. Demchenko ◽  
Albert E. Boso ◽  
Thomas J. O'Neill ◽  
Peter B. Bennett ◽  
Claude A. Piantadosi
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Methyl Ester ◽  
No Production ◽  
No Donors ◽  
Mk 801 ◽  
Neuronal Excitation ◽  
Synthase Inhibitor ◽  
Electroencephalogram Eeg

We have tested the hypothesis that cerebral nitric oxide (NO) production is involved in hyperbaric O2 (HBO2) neurotoxicity. Regional cerebral blood flow (rCBF) and electroencephalogram (EEG) were measured in anesthetized rats during O2 exposure to 1, 3, 4, and 5 ATA with or without administration of the NO synthase inhibitor ( N ω-nitro-l-arginine methyl ester), l-arginine, NO donors, or the N-methyl-d-aspartate receptor inhibitor MK-801. After 30 min of O2 exposure at 3 and 4 ATA, rCBF decreased by 26–39% and by 37–43%, respectively, and was sustained for 75 min. At 5 ATA, rCBF decreased over 30 min in the substantia nigra by one-third but, thereafter, gradually returned to preexposure levels, preceding the onset of EEG spiking activity. Rats pretreated with N ω-nitro-l-arginine methyl ester and exposed to HBO2 at 5 ATA maintained a low rCBF. MK-801 did not alter the cerebrovascular responses to HBO2at 5 ATA but prevented the EEG spikes. NO donors increased rCBF in control rats but were ineffective during HBO2 exposures. The data provide evidence that relative lack of NO activity contributes to decreased rCBF under HBO2, but, as exposure time is prolonged, NO production increases and augments rCBF in anticipation of neuronal excitation.

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