scholarly journals The Involvement of Arginase and Nitric Oxide Synthase in Breast Cancer Development: Arginase and NO Synthase as Therapeutic Targets in Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Nikolay Avtandilyan ◽  
Hayarpi Javrushyan ◽  
Gayane Petrosyan ◽  
Armen Trchounian
Keyword(s):  
Breast Cancer ◽  
Nitric Oxide ◽  
Human Serum ◽  
No Synthase ◽  
Cancer Development ◽  
Cancer Cell Proliferation ◽  
Antitumor Effects ◽  
Before And After ◽  
Oxide Synthase ◽  
Burk Plot

It is well established that, during development of malignancies, metabolic changes occur, including alterations of enzyme activities and isoenzyme expression. Arginase and nitric oxide (NO) synthase (NOS) are two of those enzymes considered to be involved in tumorigenesis. The goal of this article was to study the involvement of arginase and NOS in the development of different stages of breast cancer. Our results have shown that human serum arginase activity and NO (resp., and NOS activity) and polyamines quantities increased in parallel with cancer stage progression and decreased after neoadjuvant chemotherapy. For breast cancer, the only isoenzyme of arginase expressed in serum before and after chemotherapy was in a cationic form. The data of Lineweaver-Burk plot with aKmvalue of 2 mM was calculated, which is characteristic for human liver type isoform of arginase. During electrophoresis at pH 8.9, the enzyme exhibited high electrophoretic mobility and was detected near the anode. The presented results demonstrated that arginase in human serum with breast cancer and after chemotherapy is not polymorphic. We suggest that arginase and NOS inhibition has antitumor effects on cancer development, as it can inhibit polyamines and NO levels, a precursor of cancer cell proliferation, metastasis, and tumor angiogenesis.

Systemic and regional hemodynamics after nitric oxide synthase inhibition: role of a neurogenic mechanism

1994 ◽  
Vol 267 (1) ◽  
pp. R84-R88 ◽  
Author(s):  
M. Huang ◽  
M. L. Leblanc ◽  
R. L. Hester
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Output ◽  
No Synthase ◽  
Before And After ◽  
Regional Hemodynamics ◽  
Autonomic Blockade ◽  
Infusion Of Norepinephrine ◽  
Oxide Synthase

The study tested the hypothesis that the increase in blood pressure and decrease in cardiac output after nitric oxide (NO) synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) was partially mediated by a neurogenic mechanism. Rats were anesthetized with Inactin (thiobutabarbital), and a control blood pressure was measured for 30 min. Cardiac output and tissue flows were measured with radioactive microspheres. All measurements of pressure and flows were made before and after NO synthase inhibition (20 mg/kg L-NAME) in a group of control animals and in a second group of animals in which the autonomic nervous system was blocked by 20 mg/kg hexamethonium. In this group of animals, an intravenous infusion of norepinephrine (20-140 ng/min) was used to maintain normal blood pressure. L-NAME treatment resulted in a significant increase in mean arterial pressure in both groups. L-NAME treatment decreased cardiac output approximately 50% in both the intact and autonomic blocked animals (P < 0.05). Autonomic blockade alone had no effect on tissue flows. L-NAME treatment caused a significant decrease in renal, hepatic artery, stomach, intestinal, and testicular blood flow in both groups. These results demonstrate that the increase in blood pressure and decreases in cardiac output and tissue flows after L-NAME treatment are not dependent on a neurogenic mechanism.

scholarly journals Blockade of neuronal nitric oxide synthase alters the baroreflex control of heart rate in the rabbit

1998 ◽  
Vol 274 (1) ◽  
pp. R181-R186 ◽  
Author(s):  
Hiroshi Murakami ◽  
Jun-Li Liu ◽  
Hirohito Yoneyama ◽  
Yasuhiro Nishida ◽  
Kenji Okada ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
No Synthase ◽  
Baroreflex Control ◽  
Neuronal No Synthase ◽  
Significant Difference ◽  
Before And After ◽  
Synthase Inhibitor ◽  
Oxide Synthase

In previous studies we used N G-nitro-l-arginine (l-NNA) to investigate the role of nitric oxide (NO) in baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA).l-NNA increased resting mean arterial pressure (MAP), decreased HR, and did not change or slightly decreased RSNA. These changes complicated the assessment of the central effects of NO on the baroreflex control of HR and RSNA. Therefore, in the present study the effects of the relatively selective neuronal NO synthase inhibitor 7-nitroindazole (7-NI) on the baroreflex control of HR and RSNA were investigated in rabbits. Intraperitoneal injection of 7-NI (50 mg/kg) had no effect on resting HR, MAP, or RSNA. 7-NI significantly reduced the lower plateau of the HR-MAP baroreflex curve from 140 ± 4 to 125 ± 4 and from 177 ± 10 to 120 ± 9 beats/min in conscious and anesthetized preparations, respectively ( P < 0.05). In contrast, there was no significant difference in the RSNA-MAP curves before and after 7-NI administration in conscious or anesthetized preparations. These data suggest that blockade of neuronal NO synthase influences baroreflex control of HR but not of RSNA in rabbits.

scholarly journals Anticancer Effect of in Vivo Inhibition of Nitric Oxide Synthase in a Rat Model of Breast Cancer

2021 ◽  
Author(s):  
Nikolay Avtandilyan ◽  
Hayarpi Javrushyan ◽  
Mikayel Ginovyan ◽  
Anna Karapetyan ◽  
Armen Trchounian
Keyword(s):  
Breast Cancer ◽  
Nitric Oxide ◽  
Cancer Treatment ◽  
No Synthase ◽  
Antitumor Effects ◽  
Blood Concentrations ◽  
Anti Cancer ◽  
Cancer Agent ◽  
Synthase Inhibitor

Abstract High expression of nitric oxide (NO)-synthase has been found in different cancers like cervical, breast, and central nervous system. NO-synthase activity inhibition has been suggested as a possible tool to prevent breast cancer. The anti-tumor therapeutic effect of L-nitro arginine methyl ester (L-NAME) in vivo remains understudied. Here we hypothesized that NOS inhibition by L-NAME has some antitumor effects on breast cancer development as it inhibits NO levels, which is a pathophysiological modulator of cell proliferation, cell cycle arrest, apoptosis, and angiogenesis. We utilized a novel anti-cancer treatment model by the administration of NO-synthase inhibitor L-NAME (30 mg/kg in a day, intraperitoneal), injected every third day for five weeks (in parallel to tumors evolution) in opposition to high activity of NOS during 7,12-dimethylbenz[a]anthracene-induced breast tumor in rats in vivo. The blood concentrations of nitrite anions, polyamines, malondialdehyde, NH4+ levels, and arginase activity decreased in DMBA+L-NAME-treated rats compared with DMBA rats. The reduction of these compounds also affects the decrease of the mortality rate of rats, tumor number, weight and volume, and the histopathological grade of breast cancer. Treatment with L-NAME showed increases in time of tumor incidence and body weight compared with DMBA-cancer rats. Therefore, the co-administration of L-NAME influences as a potent anti-cancer agent to treat breast cancer and can lead to the development of therapeutic methods for cancers in the future.

scholarly journals Role of Endothelial Nitric Oxide Synthase in Hypoxia-Induced Pial Artery Dilation

1998 ◽  
Vol 18 (5) ◽  
pp. 531-538 ◽  
Author(s):  
Michael J. Wilderman ◽  
William M. Armstead
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Methionine Enkephalin ◽  
Cranial Window ◽  
Pial Artery ◽  
Endothelial No Synthase ◽  
Before And After ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Nitric oxide (NO) contributes to hypoxia-induced pial artery dilation, at least in part, through the formation of cGMP and the subsequent release of methionine enkephalin and leucine enkephalin in the newborn pig. In separate studies, these opioids also were observed to elicit NO-dependent pial artery dilation, whereas light/dye endothelial injury reduced hypoxic pial dilation. The current study was designed to investigate the role of the endothelial isoform of NO synthase in hypoxic pial dilation, associated opioid release, and opioid dilation in piglets equipped with a closed cranial window. N-iminoethyl-l-ornithine (l-NIO) (10−6 mol/L), an antagonist that may have greater endothelial NO synthase inhibitory selectivity, had no effect on dilation elicited by hypoxia (Po2 ≈ 35 mm Hg) (24 ± 2 versus 24 ± 2% in the absence and presence of l-NIO, respectively, n = 8). Hypoxic dilation was accompanied by increased CSF cGMP, which also was unchanged in the presence of l-NIO (394 ± 19 and 776 ± 63 versus 323 ± 13 and 739 ± 25 fmol/mL for control and hypoxia in the absence and presence of l-NIO, respectively, n = 6). Additionally, hypoxic pial dilation was associated with increased CSF methionine enkephalin, which also was unchanged in the presence of l-NIO (992 ± 73 and 2469 ± 197 versus 984 ± 18 and 2275 ± 185 pg/mL, respectively, n = 6). In contrast, methionine enkephalin–induced dilation was blocked by l-NIO (6 ± 1, 10 ± 1, and 16 ± 1 versus 1 ± 1, 1 ± 1, and 2 ± 1% for 10−10, 10−8, 10−6 mol/L methionine enkephalin, respectively, before and after l-NIO, n = 8). Substance P–induced pial dilation was blunted by l-NIO, whereas responses to sodium nitroprusside and N-methyl-d-aspartate were unchanged. These data indicate that endothelial NO synthase contributes to opioid-induced pial artery dilation but not hypoxia-induced dilation. Additionally, these data suggest that neuronally derived NO contributes to hypoxic pial dilation.

The Effect on Health of Some Cardiovascular Risk Factors

2017 ◽  
Vol 68 (10) ◽  
pp. 2237-2242
Author(s):  
Germaine Savoiu Balint ◽  
Mihaiela Andoni ◽  
Ramona Amina Popovici ◽  
Laura Cristina Rusu ◽  
Ioana Citu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Reactivity ◽  
Vascular Wall ◽  
Dose Effect ◽  
Organ Bath ◽  
Before And After ◽  
Specific Receptors ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Relaxing Response

Arterial endothelium produces a large ramge of active factors which are indispensable for modulation of vasomotor tone and maintenance of vascular wall integrity. From these factors, nitric oxide (NO), wich is released by the endothelial cells as a response to acetylcholine or adenosine action on specific receptors, plays an important role.NO is the result of oxidation process of L-arginine into L-citrulline, under the action of endothelial nitric oxide synthase (NOSe), wich is activated by intracelluar Ca2+ - calmodulin complex . Our study, performed in isolated organ bath, analyzed vascular reactivity of 12 guinea pigs� thoracic aorta rings. After phenylephrine -PHE 10-5 mol/L precontraction, the dose-effect curves for acetylcoline � ACH, adenosine 5� phosphate - 5�ADP and sodium nitroprusside � SNP were determined, before and after incubation of preparation, for 1 hour, with 5% hydrosoluble cigarettes smoke extract (CSE). Statistic analysis, performed with the use of t pair test and ANOVA parametric test, showed that incubation of vascular preparation with 5% CSE has increased the contractile response to PHE 10-5 mol/L (p[0.05), has reduced the endothelium-dependent relaxing response to ATP 10-5 mol/L (p[0.001) and 5�ADP 10-5 molo/L (p[0.001), but has not significantly modified the endothelium-independent relaxing response to SNP 10-5 mol/L (p=0.05). As a conclusion, vascular rings incubation with 5% CSE induced a decrease of endothelium NO synthesis under the action of AXH and 5�ADP, but did not change the smooth muscle fiber respomse in the presence of NO released by SNP.

Acute compensation to abrupt occlusion of rat femoral artery is prevented by NO synthase inhibitors

1994 ◽  
Vol 267 (6) ◽  
pp. H2523-H2530 ◽  
Author(s):  
J. L. Unthank ◽  
J. C. Nixon ◽  
M. C. Dalsing
Keyword(s):  
Femoral Artery ◽  
Arterial Occlusion ◽  
Artery Occlusion ◽  
No Synthase ◽  
Artery Blood Flow ◽  
Relaxing Factor ◽  
Femoral Artery Occlusion ◽  
Before And After ◽  
Endothelium Derived Relaxing Factor ◽  
Oxide Synthase

The hemodynamic significance of endothelium-derived relaxing factor (EDRF)-mediated mechanisms in vascular responses to abrupt rat femoral artery occlusion was investigated. Temporary arterial occlusion was produced before and after inhibition of nitric oxide synthase by N omega-nitro-L-arginine methyl ester (L-NAME) or NG-monomethyl-L-arginine (L-NMMA). Iliac artery blood flow and arterial pressures proximal and distal to the occlusion were measured. Normal vascular compensation included a return of resistance to preocclusion levels and a rise in distal pressure to a plateau within 5 min postocclusion. After treatment with L-NAME and L-NMMA, postocclusion resistance remained elevated by 53 and 36%, respectively. Collateral dilation after occlusion, as indicated by the rise in distal pressure, was prevented by L-NAME but not L-NMMA. Increases in adrenergic tone and mean arterial pressure by phenylephrine did not prevent compensation, suggesting the effects of L-NAME and L-NMMA did not result from elevated sympathetic activation or pressure. The results are consistent with the hypothesis that the stimulated release of endothelium-derived relaxing factor mediates the acute vascular compensation to abrupt arterial occlusion.

scholarly journals Oral atorvastatin therapy increases nitric oxide-dependent cutaneous vasodilation in humans by decreasing ascorbate-sensitive oxidants

2011 ◽  
Vol 301 (3) ◽  
pp. R763-R768 ◽  
Author(s):  
Lacy A. Holowatz ◽  
W. Larry Kenney
Keyword(s):  
Nitric Oxide ◽  
Local Heating ◽  
Oxidant Stress ◽  
Microvascular Dysfunction ◽  
Local Skin ◽  
Cutaneous Vasodilation ◽  
Before And After ◽  
Atorvastatin Therapy ◽  
Oxide Synthase ◽  
Cutaneous Vascular Conductance

Elevated low-density lipoproteins (LDL) are associated with cutaneous microvascular dysfunction partially mediated by increased arginase activity, which is decreased following a systemic atorvastatin therapy. We hypothesized that increased ascorbate-sensitive oxidant stress, partially mediated through uncoupled nitric oxide synthase (NOS) induced by upregulated arginase, contributes to cutaneous microvascular dysfunction in hypercholesterolemic (HC) humans. Four microdialysis fibers were placed in the skin of nine HC (LDL = 177 ± 6 mg/dl) men and women before and after 3 mo of a systemic atorvastatin intervention and at baseline in nine normocholesterolemic (NC) (LDL = 95 ± 4 mg/dl) subjects. Sites served as control, NOS inhibited, L-ascorbate, and arginase-inhibited+L-ascorbate. Skin blood flow was measured while local skin heating (42°C) induced NO-dependent vasodilation. After the established plateau in all sites, 20 mM ≪ngname≫ was infused to quantify NO-dependent vasodilation. Data were normalized to maximum cutaneous vascular conductance (CVC) (sodium nitroprusside + 43°C). The plateau in vasodilation during local heating (HC: 78 ± 4 vs. NC: 96 ± 2% CVCmax, P < 0.01) and NO-dependent vasodilation (HC: 40 ± 4 vs. NC: 54 ± 4% CVCmax, P < 0.01) was reduced in the HC group. Acute L-ascorbate alone (91 ± 5% CVCmax, P < 0.001) or combined with arginase inhibition (96 ± 3% CVCmax, P < 0.001) augmented the plateau in vasodilation in the HC group but not the NC group (ascorbate: 96 ± 2; combo: 93 ± 4% CVCmax, both P > 0.05). After the atorvastatin intervention NO-dependent vasodilation was augmented in the HC group (HC postatorvastatin: 64 ± 4% CVCmax, P < 0.01), and there was no further effect of ascorbate alone (58 ± 4% CVCmax, P > 0.05) or combined with arginase inhibition (67 ± 4% CVCmax, P > 0.05). Increased ascorbate-sensitive oxidants contribute to hypercholesteromic associated cutaneous microvascular dysfunction which is partially reversed with atorvastatin therapy.

scholarly journals Antioxidants and Gene Regulation: The Effects of Vitamins C and E on Estrogen Receptors

Elements ◽  
2006 ◽  
Vol 2 (1) ◽  
Author(s):  
Jeong Ho Nam
Keyword(s):  
Breast Cancer ◽  
Nitric Oxide ◽  
Estrogen Receptor ◽  
Breast Cancer Cells ◽  
Past Research ◽  
Receptor Expression ◽  
Cancer Development ◽  
Nitric Oxide Release ◽  
Gene Level ◽  
Estrogen Binding

Research shows that estrogen binding to its receptor plays a role in breast cancer development and that antioxidants possibly mitigate this effect. Past research examined whether various treatments lead to accelerated cell division, but characterization and comparison of the effects of different treatments on gene level expression of the receptor was not accomplished. Initially, the effect of antioxidants on the estrogen receptor expression was investigated, revealing the presence of Vitamins C and E on nitric oxide release (a possible cancer reduction agent) stimulated by estrogen acting on the surface estrogen receptor of breast cancer cells was observed. Generally, Vitamin E was most effective for improving nitric oxide release.

Potentiation to vasodilators by nitric oxide synthase blockade in superior mesenteric but not hepatic artery

1997 ◽  
Vol 272 (3) ◽  
pp. G507-G514 ◽  
Author(s):  
M. P. Macedo ◽  
W. W. Lautt
Keyword(s):  
Nitric Oxide ◽  
Hepatic Artery ◽  
Organ Specificity ◽  
No Production ◽  
Compensatory Mechanism ◽  
Basal Tone ◽  
Before And After ◽  
Organ Specific ◽  
Pentobarbital Sodium Anesthesia ◽  
Oxide Synthase

Our objective was to determine the vasodilator effect of adenosine and isoproterenol on the hepatic artery (HA) and superior mesenteric artery (SMA) before and after blockade of nitric oxide (NO) production to evaluate the possibility of organ specificity. Vascular circuits supplied blood flow to the liver or intestine in cats under pentobarbital sodium anesthesia. The NO synthase (NOS) antagonist N(G)-nitro-L-arginine methyl ester (L-NAME; 2.5 mg/kg iv) increased arterial pressure from 106.4 +/- 7.6 to 141.4 +/- 8.1 mmHg and raised basal vascular tone in the SMA but not in the HA. The NOS substrate L-arginine (75 mg/kg) reversed these effects. The decrease in perfusion pressure in response to adenosine was 51.7 +/- 2.9, 135.2 +/- 6.1, and 16.7 +/- 2.4 mmHg, respectively, for control and after L-NAME and L-arginine. Isoproterenol was also potentiated in the SMA. Adenosine and isoproterenol were not potentiated in the HA by L-NAME. Potentiation did not occur when HA or SMA basal tone was elevated by norepinephrine. In conclusion, L-NAME increased basal tone for the SMA and potentiated the dilation induced by adenosine and isoproterenol in the SMA but not in the HA. This study provides evidence that there is a highly organ-specific compensatory mechanism in which the absence of NO promotes potentiation of other vasodilators.

Release of nitric oxide and prostaglandin H2 to acetylcholine in skeletal muscle venules

1997 ◽  
Vol 272 (6) ◽  
pp. H2541-H2546 ◽  
Author(s):  
G. Dornyei ◽  
G. Kaley ◽  
A. Koller
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Perfusion Pressure ◽  
Thromboxane A2 ◽  
No Synthase ◽  
Gracilis Muscle ◽  
Vasoactive Agents ◽  
Before And After ◽  
Higher Doses

The role of endothelium in regulating venular resistance is not well characterized. Thus we aimed to elucidate the endothelium-derived factors involved in the mediation of responses of rat gracilis muscle venules to acetylcholine (ACh) and other vasoactive agents. Changes in diameter of perfusion pressure (7.5 mmHg)- and norepinephrine (10(-6) M)-constricted venules (approximately 225 microns in diam) to cumulative doses of ACh (10(-9) to 10(-4) M) and sodium nitroprusside (SNP, 10(-9) to 10(-4) M), before and after endothelium removal or application of various inhibitors, were measured. Lower doses of ACh elicited dilations (up to 42.1 +/- 4.7%), whereas higher doses of ACh resulted in smaller dilations or even constrictions. Endothelium removal abolished both ACh-induced dilation and constriction. In the presence of indomethacin (2.8 x 10(-5) M), a cyclooxygenase blocker, or SQ-29548 (10(-6) M), a thromboxane A2-prostaglandin H2 (PGH2) receptor antagonist, higher doses of ACh caused further dilation (up to 72.7 +/- 7%) instead of constriction. Similarly, lower doses of arachidonic acid (10(-9) to 10(-6) M) elicited dilations that were diminished at higher doses. These reduced responses were, however, reversed to substantial dilation by SQ-29548. The nitric oxide (NO) synthase blocker, N omega-nitro-L-arginine (L-NNA, 10(-4) M), significantly reduced the dilation to ACh (from 30.6 +/- 5.5 to 5.4 +/- 1.4% at 10(-6) M ACh). In contrast, L-NNA did not affect dilation to SNP. Thus ACh elicits the release of both NO and PGH2 from the venular endothelium.

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