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.

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.

Accumulation of HIF-1α under the influence of nitric oxide

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 1009-1015 ◽  
Author(s):  
Katrin Britta Sandau ◽  
Joachim Fandrey ◽  
Bernhard Brüne
Keyword(s):  
Nitric Oxide ◽  
Close Correlation ◽  
No Synthase ◽  
Protein Stabilization ◽  
Time Dependent ◽  
Target Cells ◽  
Dependent Manner ◽  
No Donor ◽  
No Donors ◽  
The Impact

Abstract The key player for adaptation to reduced oxygen availability is the transcription factor hypoxia-inducible factor 1 (HIF-1), composed of the redox-sensitive HIF-1α and the constitutively expressed HIF-1β subunits. Under normoxic conditions, HIF-1α is rapidly degraded, whereas hypoxia, CoCl2, or desferroxamine promote protein stabilization, thus evoking its transcriptional activity. Because HIF-1 is regulated by reactive oxygen species, investigation of the impact of reactive nitrogen species was intended. By using different nitric oxide (NO) donors, dose- and time-dependent HIF-1α accumulation in close correlation with the release of NO from chemically distinct NO donors was established. Intriguingly, small NO concentrations induced a faster but transient HIF-1α accumulation than higher doses of the same NO donor. In contrast, NO attenuated up-regulation of HIF-1α evoked by CoCl2 in a concentration- and time-dependent manner, whereas the desferroxamine-elicited HIF-1α signal remained unaltered. To demonstrate an autocrine or paracrine signaling function of NO, we overexpressed the inducible NO synthase and used a coculture system of activated macrophages and tubular cells. Expression of the NO synthase induced HIF-1α accumulation, which underscored the role of NO as an intracellular activator for HIF-1. In addition, macrophage-derived NO triggered HIF-1α up-regulation in LLC-PK1 target cells, which points to intercellular signaling properties of NO in achieving HIF-1 accumulation. Our results show that NO does not only modulate the HIF-1 response under hypoxic conditions, but it also functions as a HIF-1 inducer. We conclude that accumulation of HIF-1 occurs during hypoxia but also under inflammatory conditions that are characterized by sustained NO formation.

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.

scholarly journals Glyoxalase I is a novel nitric-oxide-responsive protein

1999 ◽  
Vol 344 (3) ◽  
pp. 837-844 ◽  
Author(s):  
Atsushi MITSUMOTO ◽  
Kwi-Ryeon KIM ◽  
Genichiro OSHIMA ◽  
Manabu KUNIMOTO ◽  
Katsuya OKAWA ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Culture Medium ◽  
Molecular Mechanisms ◽  
Peptide Mapping ◽  
Glyoxalase I ◽  
Dependent Manner ◽  
Human Endothelial Cells ◽  
Native Form ◽  
No Donors ◽  
Dose Dependent

To clarify the molecular mechanisms of nitric oxide (NO) signalling, we examined the NO-responsive proteins in cultured human endothelial cells by two-dimensional (2D) PAGE. Levels of two proteins [NO-responsive proteins (NORPs)] with different pI values responded to NO donors. One NORP (pI 5.2) appeared in response to NO, whereas another (pI 5.0) disappeared. These proteins were identified as a native form and a modified form of human glyoxalase I (Glox I; EC 4.4.1.5) by peptide mapping, microsequencing and correlation between the activity and the isoelectric shift. Glox I lost activity in response to NO, and all NO donors tested inhibited its activity in a dose-dependent manner. Activity and normal electrophoretic mobility were restored by dithiothreitol and by the removal of sources of NO from the culture medium. Glox I was selectively inactivated by NO; compounds that induce oxidative stress (H2O2, paraquat and arsenite) failed to inhibit this enzyme. Our results suggest that NO oxidatively modifies Glox I and reversibly inhibits the enzyme's activity. The inactivation of Glox I by NO was more effective than that of glyceraldehyde-3-phosphate dehydrogenase (G3PDH), another NO-sensitive enzyme. Thus Glox I seems to be a novel NO-responsive protein that is more sensitive to NO than G3PDH.

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.

Role of Nitric Oxide towards Vasodilator Effects of Substance P and ATP in Human Forearm Vessels

1997 ◽  
Vol 92 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Masanari Shiramoto ◽  
Tsutomu Imaizumi ◽  
Yoshitaka Hirooka ◽  
Toyonari Endo ◽  
Takashi Namba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Dependent Manner ◽  
Human Forearm ◽  
Before And After ◽  
Dose Dependent

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-l-arginine (4 or 8 μmol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of l-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-l-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of l-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation. 4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.

Nitric Oxide: Potential of NO Donors and NO Synthase Inhibitors for the Treatment of Pain

Analgesics ◽  
2005 ◽  
pp. 555-566
Author(s):  
Corinna Maul ◽  
Hagen-Heinrich Hennies ◽  
Bernd Sundermann
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
No Donors

Compensatory role of NO in cerebral circulation of piglets chronically treated with indomethacin

2002 ◽  
Vol 282 (2) ◽  
pp. R400-R410 ◽  
Author(s):  
Yifan Zhang ◽  
C. W. Leffler
Keyword(s):  
Nitric Oxide ◽  
Cerebrospinal Fluid ◽  
Methyl Ester ◽  
Cerebral Circulation ◽  
No Synthase ◽  
Inhibitory Effects ◽  
Circulatory Control ◽  
Pial Arterioles ◽  
Indomethacin Treatment

We hypothesize that inhibitory effects exist between prostanoids and nitric oxide (NO) in their contributions to cerebral circulation. Piglets (1–4 days old) were divided into three chronically treated (6–8 days) groups: control piglets, piglets treated with indomethacin (75 mg/day), and piglets treated with N ω-nitro-l-arginine methyl ester (l-NAME, 100 mg · kg−1 · day−1). Pial arterioles dilated in response to hypercapnia similarly among the three groups (41 ± 4, 40 ± 6, and 45 ± 11%). Cerebrospinal fluid cAMP increased in control piglets, while cGMP increased in indomethacin-treated piglets. l-NAME, but not 7-nitroindazole, inhibited the response to hypercapnia only in indomethacin-treated piglets (40 ± 6 vs. 17 ± 5%). Topical sodium nitroprusside or iloprost restored dilation in response to hypercapnia. Similar results were obtained when the dilator was bradykinin. Pial arterioles of control and l-NAME-treated piglets constricted in response to ACh (−24 ± 3%). However, those of indomethacin-treated piglets dilated in response to ACh (15 ± 2%). This dilation was inhibited by l-NAME. NO synthase activity, but not endothelial NO synthase expression, increased after chronic indomethacin treatment. These data suggest that chronic inhibition of cyclooxygenase can increase the contribution of NO to cerebrovascular circulatory control in piglets.

scholarly journals Endogenous vascular remodeling in ischemic skeletal muscle: a role for nitric oxide

2003 ◽  
Vol 94 (3) ◽  
pp. 935-940 ◽  
Author(s):  
John B. Buckwalter ◽  
Valerie C. Curtis ◽  
Zoran Valic ◽  
Stephen B. Ruble ◽  
Philip S. Clifford
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Methyl Ester ◽  
Vascular Remodeling ◽  
Treated Group ◽  
No Synthase ◽  
No Production ◽  
Ischemic Limb ◽  
Time Flow

To test the hypothesis that nitric oxide (NO) production is essential for endogenous vascular remodeling in ischemic skeletal muscle, 22 New Zealand White rabbits were chronically instrumented with transit-time flow probes on the common iliac arteries and underwent femoral ligation to produce unilateral hindlimb ischemia. Iliac blood flow and arterial pressure were recorded at rest and during a graded exercise test. An osmotic pump connected to a femoral arterial catheter continuously delivered N-nitro-l-arginine methyl ester (a NO synthase inhibitor) or a control solution ( N-nitro-d-arginine methyl ester or phenylephrine) to the ischemic limb over a 2-wk period. At 1, 3, and 6 wk after femoral ligation, maximal treadmill exercise blood flow in the ischemic limb was reduced compared with baseline in each group. However, maximal exercise blood flow was significantly ( P < 0.05) lower in the l-NAME-treated group than in controls for the duration of the study: 48 ± 4 vs. 60 ± 5 ml/min at 6 wk. Consistent with the reduction in maximal blood flow response, the duration of voluntary exercise was also substantially ( P < 0.05) shorter in thel-NAME-treated group: 539 ± 67 vs. 889 ± 87 s. Resting blood flow was unaffected by femoral ligation in either group. The results of this study show that endogenous vascular remodeling, which partially alleviated the initial deficit in blood flow, was interrupted by NO synthase inhibition. Therefore, we conclude that NO is essential for endogenous collateral development and angiogenesis in ischemic skeletal muscle in the rabbit.

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