scholarly journals Vascular acetylcholine response during chronic NO synthase inhibition: in vivo versus in vitro

1995 ◽  
Vol 30 (1) ◽  
pp. 122-129 ◽  
Author(s):  
A. Zanchi ◽  
J. F. Aubert ◽  
H. R. Brunner ◽  
B. Waeber
Keyword(s):  
No Synthase

scholarly journals Sevoflurane Promotes Bactericidal Properties of Macrophages through Enhanced Inducible Nitric Oxide Synthase Expression in Male Mice

2019 ◽  
Vol 131 (6) ◽  
pp. 1301-1315 ◽  
Author(s):  
Thomas J. Gerber ◽  
Valérie C. O. Fehr ◽  
Suellen D. S. Oliveira ◽  
Guochang Hu ◽  
Randal Dull ◽  
...  
Keyword(s):  
Early Stage ◽  
No Synthase ◽  
Control Group ◽  
Male Mice ◽  
Proinflammatory Response ◽  
E Coli ◽  
Inducible No Synthase ◽  
Bactericidal Properties

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Sevoflurane with its antiinflammatory properties has shown to decrease mortality in animal models of sepsis. However, the underlying mechanism of its beneficial effect in this inflammatory scenario remains poorly understood. Macrophages play an important role in the early stage of sepsis as they are tasked with eliminating invading microbes and also attracting other immune cells by the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Thus, the authors hypothesized that sevoflurane mitigates the proinflammatory response of macrophages, while maintaining their bactericidal properties. Methods Murine bone marrow–derived macrophages were stimulated in vitro with lipopolysaccharide in the presence and absence of 2% sevoflurane. Expression of cytokines and inducible NO synthase as well as uptake of fluorescently labeled Escherichia coli (E. coli) were measured. The in vivo endotoxemia model consisted of an intraperitoneal lipopolysaccharide injection after anesthesia with either ketamine and xylazine or 4% sevoflurane. Male mice (n = 6 per group) were observed for a total of 20 h. During the last 30 min fluorescently labeled E. coli were intraperitoneally injected. Peritoneal cells were extracted by peritoneal lavage and inducible NO synthase expression as well as E. coli uptake by peritoneal macrophages was determined using flow cytometry. Results In vitro, sevoflurane enhanced lipopolysaccharide-induced inducible NO synthase expression after 8 h by 466% and increased macrophage uptake of fluorescently labeled E. coli by 70% compared with vehicle-treated controls. Inhibiting inducible NO synthase expression pharmacologically abolished this increase in bacteria uptake. In vivo, inducible NO synthase expression was increased by 669% and phagocytosis of E. coli by 49% compared with the control group. Conclusions Sevoflurane enhances phagocytosis of bacteria by lipopolysaccharide-challenged macrophages in vitro and in vivo via an inducible NO synthase–dependent mechanism. Thus, sevoflurane potentiates bactericidal and antiinflammatory host-defense mechanisms in endotoxemia.

Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium

1996 ◽  
Vol 270 (1) ◽  
pp. H411-H415 ◽  
Author(s):  
L. Morbidelli ◽  
C. H. Chang ◽  
J. G. Douglas ◽  
H. J. Granger ◽  
F. Ledda ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Growth Factor ◽  
No Synthase ◽  
Mitogenic Effect ◽  
Microvascular Endothelium ◽  
Proliferative Effect

Vascular endothelial growth factor (VEGF) is a secreted protein that is a specific growth factor for endothelial cells. We have recently demonstrated that nitric oxide (NO) donors and vasoactive peptides promoting NO-mediated vasorelaxation induce angiogenesis in vivo as well as endothelial cell growth and motility in vitro; in contrast, inhibitors of NO synthase suppress angiogenesis. In this study we investigated the role of NO in mediating the mitogenic effect of VEGF on cultured microvascular endothelium isolated from coronary postcapillary venules. VEGF induced a dose-dependent increase in cell proliferation and DNA synthesis. The role of NO was determined by monitoring proliferation or guanosine 3',5'-cyclic monophosphate (cGMP) levels in the presence and absence of NO synthase blockers. The proliferative effect evoked by VEGF was reduced by pretreatment of the cells with NO synthase inhibitors. Exposure of the cells to VEGF induced a significant increment in cGMP levels. This effect was potentiated by superoxide dismutase addition and was abolished by NO synthase inhibitors. VEGF stimulates proliferation of postcapillary endothelial cells through the production of NO and cGMP accumulation.

scholarly journals Reciprocal regulation of the nitric oxide and cyclooxygenase pathway in pathophysiology: relevance and clinical implications

2013 ◽  
Vol 304 (7) ◽  
pp. R473-R487 ◽  
Author(s):  
Daniela Salvemini ◽  
Sangwon F. Kim ◽  
Vincenzo Mollace
Keyword(s):  
Nitric Oxide ◽  
Arachidonic Acid ◽  
State Of The Art ◽  
No Synthase ◽  
In Vivo Studies ◽  
Clinical Implications ◽  
Reciprocal Regulation ◽  
Receptor Targets

The nitric oxide (NO) and cyclooxygenase (COX) pathways share a number of similarities. Nitric oxide is the mediator generated from the NO synthase (NOS) pathway, and COX converts arachidonic acid to prostaglandins, prostacyclin, and thromboxane A2. Two major forms of NOS and COX have been identified to date. The constitutive isoforms critically regulate several physiological states. The inducible isoforms are overexpressed during inflammation in a variety of cells, producing large amounts of NO and prostaglandins, which may underlie pathological processes. The cross-talk between the COX and NOS pathways was initially reported by Salvemini and colleagues in 1993, when they demonstrated in a series of in vitro and in vivo studies that NO activates the COX enzymes to produce increased amounts of prostaglandins. Those studies led to the concept that COX enzymes represent important endogenous “receptor” targets for amplifying or modulating the multifaceted roles of NO in physiology and pathology. Since then, numerous studies have furthered our mechanistic understanding of these interactions in pathophysiological settings and delineated potential clinical outcomes. In addition, emerging evidence suggests that the canonical nitroxidative species (NO, superoxide, and/or peroxynitrite) modulate biosynthesis of prostaglandins through non-COX-related pathways. This article provides a comprehensive state-of-the art overview in this area.

Age-related changes in carotid vascular responses to adenosine and nitric oxide in the rat: in vitro and in vivo studies

2010 ◽  
Vol 109 (2) ◽  
pp. 305-313 ◽  
Author(s):  
Nisreen Mansour Omar ◽  
Janice M. Marshall
Keyword(s):  
Carotid Artery ◽  
Cerebral Autoregulation ◽  
No Synthase ◽  
Aged Rats ◽  
Middle Aged ◽  
Juvenile Rats ◽  
Age Related ◽  
Carotid Circulation

We investigated how the ability of adenosine to release nitric oxide (NO) from carotid artery in vitro, and dilator responses evoked in carotid circulation in vivo by systemic infusion of adenosine, change with age in rats of 4–5, 10–12, and 42–44 wk (juvenile, mature, and middle aged). A secondary aim was to follow age-related changes in carotid/cerebral autoregulation. In opened carotid artery, graded doses of adenosine evoked graded increases in NO output measured with a NO sensor that were greater in mature and middle-aged than juvenile rats. Infusion of adenosine to reduce mean arterial pressure (ABP) to ∼60 mmHg increased carotid vascular conductance (CVC) in all groups, but the increase was larger in mature rats; carotid blood flow (CBF) was unchanged in juvenile, increased in mature, but fell in 4/8 middle-aged rats. The NO synthase inhibitor nitro l-arginine methyl ester (l-NAME; 10 mg/kg iv) increased baseline ABP in all groups but caused larger percentage reductions in baseline CVC and CBF in mature and middle-aged than juvenile rats. Thereafter, the adenosine-evoked increase in CVC was unchanged in juvenile and middle-aged rats, yet CBF remained constant in juvenile but increased in middle-aged rats. In mature rats, the evoked increases in CVC and CBF were attenuated and further attenuated by l-NAME at 30 mg/kg. We propose that the ability of adenosine to release NO and cause vasodilation in the carotid artery and its circulation is greater in mature, than juvenile or middle-aged rats, but NO has greater tonic dilator influence in carotid circulation of mature and middle-aged than juvenile rats. By middle age, the lower limit of cerebral autoregulation has increased such that the tonic dilator influence of NO on ABP and CVC limits autoregulation of CBF to depressor responses. However, partial NO synthase inhibition overcomes this impairment, raising baseline ABP and allowing adenosine-evoked increases in CVC to increase CBF.

Endothelial nitric oxide synthase plays a minor role in inhibition of arterial thrombus formation

2005 ◽  
Vol 93 (06) ◽  
pp. 1161-1167 ◽  
Author(s):  
Burcin Özüyaman ◽  
Susanne Küsters ◽  
Elisabeth Kirchhoff ◽  
Rüdiger Scharf ◽  
Jürgen Schrader ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Thrombus Formation ◽  
Surface Expression ◽  
No Synthase ◽  
Minor Role ◽  
Endothelial No Synthase ◽  
Tail Tip ◽  
A Minor

SummaryEndothelial NO synthase (eNOS) expressed in the vascular en-dothelium or formed within platelets was postulated to inhibit platelet activation and aggregation. We have assessed the role of eNOS in platelet aggregation in vitro and in vivo by comparison of WT and eNOS-/- mice. Aggregometer studies revealed that collagen over a concentration range of 0.36–10 µg aggregated WT and eNOS-/- platelets to the same extent (10 µg: WT 86.7±4.7%, eNOS-/- 91±12%, n=6). Collagen treatment did not result in a significant increase in cGMP formation and VASP phosphorylation. Thrombin-induced P-selectin surface expression was unchanged in eNOS-/- platelets. In line with these findings no eNOS protein was detectable within the platelets of WT mice. In vivo, bleeding time after tail tip resection tended to be shorter in eNOS/- mice (WT: 116±35 s; eNOS-/- 109±37 s, n.s). Similarly, time to occlusion of the A.carotis after focal induction of thrombosis was 501±76 s (WT) and 457±95 s (eNOS-/-) (n.s.). These data demonstrate that eNOS-deficiency minimally affects platelet aggregation and is not associated with accelerated arterial thrombosis in vivo. Thus, in the mouse endothelial NO synthase does not play a major role in the autocrine modulation of platelet function and in thrombosis of conduit vessels in vivo.

Excessive NO production dose not account for the inhibition of hepatic gluconeogenesis in endotoxemia

1996 ◽  
Vol 271 (4) ◽  
pp. G621-G628 ◽  
Author(s):  
J. Ou ◽  
L. Molina ◽  
Y. M. Kim ◽  
T. R. Billiar
Keyword(s):  
No Synthase ◽  
No Production ◽  
Wild Type ◽  
Gapdh Activity ◽  
Nos Inhibitors ◽  
Before And After ◽  
Gluconeogenic Substrates ◽  
Fasted Rats

The pattern of inhibition of gluconeogenesis in hepatocytes was compared between endotoxemia in vivo and nitric oxide (NO) exposure in vitro. Fasted rats were injected with lipopolysaccharide (LPS; 12 mg/kg) or with vehicle alone. After 2-24 h, hepatocytes were isolated, placed in suspension, and incubated for 1 h with various gluconeogenic substrates that enter at different sites of the gluconeogenic pathway. Hepatocytes from LPS-treated rats exhibited up to a 50% decrease in gluconeogenesis for substrates that enter proximal to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) beginning at 6 h, followed by a nadir at 12 h after LPS. Although hepatocytes exposed to exogenous NO (S-nitroso-N-acetylpenicillamine) also exhibited a depressed gluconeogenesis, the pattern was not the same with inhibition in gluconeogenesis for substrates that enter the pathway both before and after GAPDH. Furthermore, when rats injected with LPS were subjected to a constant portal infusion (Alzet pump) of the NO synthase (NOS) inhibitors, NG-monomethyl-L-arginine or aminoguanidine, no changes in the LPS-induced gluconeogenesis suppression were seen. In addition, no difference in LPS-induced inhibition of gluconeogenesis was detected when hepatocytes from inducible NO synthase (NOS-2) knockout mice were compared with cells obtained from wild-type mice. Minimal decreases in GAPDH activity were measured in hepatocytes from the LPS-treated rats, whereas the activity of phosphoenol pyruvate carboxykinase (PEPCK) declined up to 40%, independent of NO synthesis. These data indicate that NO does not account for the inhibition of gluconeogenesis in endotoxemia, and they provide support for NO-independent reduction in PEPCK activity as a more plausible explanation.

Nitric oxide regulates endothelium-dependent vasodilator responses in rabbit hindquarters vascular bed in vivo

1996 ◽  
Vol 271 (1) ◽  
pp. H133-H139 ◽  
Author(s):  
G. A. Cohen ◽  
A. J. Hobbs ◽  
R. M. Fitch ◽  
M. J. Zinner ◽  
G. Chaudhuri ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Physiological Role ◽  
No Synthase ◽  
No Donor ◽  
Aortic Endothelial Cells ◽  
Vascular Bed ◽  
Feedback Modulator ◽  
Vasodilator Action

The objective of this study was to determine whether nitric oxide (NO) could function as a negative feedback modulator of endothelium-dependent vasodilation in vivo. To this end, the influence of exogenous NO on vasodilator responses in the rabbit hindquarters vascular bed was determined. Previous in vitro studies have demonstrated that NO inhibits both neuronal NO synthase from rat cerebellum as well as NO synthase derived from bovine aortic endothelial cells. The present study was conducted in the rabbit hindquarters vascular bed under conditions of constant blood flow so that changes in pressure directly reflected changes in vascular resistance. Under these in vivo conditions, the NO donor agent S-nitroso-N-acetylpenicillamine (SNAP) reversibly attenuated responses to the endothelium-dependent vasodilators, acetylcholine and bradykinin. In contrast, SNAP did not influence the endothelium-independent vasodilator response to SNAP itself or to 8-bromoguanosine 3',5'-cyclic monophosphate. These observations indicate clearly that NO interferes with endothelium-dependent vasodilator action and support the view that endogenous NO may actually play a physiological role in regulating vascular tone.

Interactions between N-methyl-D-aspartate, nitric oxide and serotonin in the control of prolactin secretion in prepubertal male rats

1997 ◽  
pp. 99-106 ◽  
Author(s):  
E Aguilar ◽  
M Tena-Sempere ◽  
R Aguilar ◽  
D Gonzalez ◽  
L Pinilla
Keyword(s):  
Nitric Oxide ◽  
Nmda Antagonist ◽  
Prolactin Secretion ◽  
No Synthase ◽  
Male Rats ◽  
Serotonin Synthesis ◽  
Mk 801

The role of N-methyl-D-aspartate (NMDA) in the control of prolactin (PRL) secretion was analysed in prepubertal male rats. In experiment 1, males of different ages were decapitated after administration of NMDA or vehicle. In experiment 2, 30-day-old males were killed at different times after administration of vehicle, NMDA, MK-801 (a non-competitive NMDA antagonist) or NMDA plus MK-801. In experiment 3, 23-day-old males were sham-orchidectomized or orchidectomized. Orchidectomized males were or were not implanted with Silastic capsules containing different amounts of testosterone. On day 30, the animals were decapitated after administration of vehicle, NMDA or MK-801. In experiment 4, 30-day-old male rats were decapitated after being injected with vehicle, NMDA, Nw-nitro-L-arginine methyl ester (NAME) (an inhibitor of nitric oxide (NO) synthase), or NMDA plus NAME. Serum PRL concentrations, and dopamine pituitary and hypothalamic content were measured. In experiment 5, males pretreated with vehicle or NAME were killed after administration of the precursor of serotonin synthesis 5-hydroxytryptophan (5-HTP), the 5-HT1 receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) or the 5-HT2 agonist (+/-) 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI). Finally, the effects of NMDA, NAME and sodium nitroprusside (SNP) were tested in dispersed adenohypophyseal cells. We found that: (1) antagonism of NMDA receptors with MK-801 decreased PRL secretion in intact, orchidectomized and orchidectomized-testosterone treated male rats; (ii) NMDA inhibited PRL release in vivo through an increase in dopamine release and this effect was potentiated by NAME and prevented by testosterone; (iii) NMDA inhibited PRL, secretion in vitro and this effect was observed in presence of both SNP and NAME; (iv) NAME blocked the stimulatory effects of 5-HTP and DOI on PRL secretion. We conclude that endogenous glutamate stimulates PRL release and that NO might have a pivotal role in the mechanisms involved in the control of PRL release, inhibiting the release of dopamine and modulating the effects of NMDA and 5-HT.

Interleukin-1β inhibits rat thyroid cell function in vivo and in vitro by an NO-independent mechanism and induces hypothyroidism and accelerated thyroiditis in diabetes-prone BB rats

1996 ◽  
Vol 151 (1) ◽  
pp. 147-157 ◽  
Author(s):  
J I Reimers ◽  
A K Rasmussen ◽  
A E Karlsen ◽  
U Bjerre ◽  
H Liang ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
No Synthase ◽  
Interleukin 1Β ◽  
Iodine Uptake ◽  
Thyroid Cell ◽  
Bb Rats ◽  
Inducible No Synthase ◽  
Rat Thyroid

Abstract Interleukin-1β has been implicated as a pathogenic factor in the development of autoimmune thyroiditis. When given for 5 days to normal non-diabetes-prone Wistar Kyoto rats, it decreased plasma concentrations of total tri-iodothyronine and thyroxine and increased plasma TSH. These effects were not prevented by co-injection of nitroarginine methyl ester or aminoguanidine, inhibitors of NO synthases. Exposure to interleukin-1β dose-dependently reduced iodine uptake in FRTL-5 cells, but had no effect on thyroglobulin secretion. Nitrite was not detected in the FRTL-5 cell culture media after exposure to interleukin-1β. However, reverse transcription PCR analysis of mRNA isolated from interleukin-1β-exposed FRTL-5 cells revealed a transitory expression of the inducible NO synthase, which was markedly lower than inducible NO synthase induction in interleukin-1β-exposed isolated rat islets of Langerhans. Co-incubation with the NO synthase inhibitor NG-monomethylarginine did not ameliorate the effect of interleukin-1β on FRTL-5 cell iodine uptake. Furthermore, we demonstrate that daily injections of interleukin-1β for 13 weeks aggravated spontaneous thyroiditis and induced severe hypothyroidism in non-diabetic diabetes-prone BB rats. The data suggest that NO does not mediate interleukin-1β-induced inhibition of rat thyroid function in vivo or in vitro in FRTL-5 cells, and the induction of hypothyroidism by interleukin-1β in diabetes-prone BB rats is speculated to be due to exacerbation of recruitment and activation of intrathyroidal mononuclear cells. Journal of Endocrinology (1996) 151, 147–157

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