Nitrogen(II) Oxide (Nitric Oxide, NO): Its Origin, Fate and Physiological Significance. A Review

1997 ◽  
Vol 62 (9) ◽  
pp. 1355-1383 ◽  
Author(s):  
Petr Vetrovsky ◽  
Gustav Entlicher
Keyword(s):  
Nitric Oxide ◽  
Superoxide Anion ◽  
De Novo ◽  
Soluble Guanylate Cyclase ◽  
No Synthase ◽  
Transcriptional Level ◽  
Immune Systems ◽  
Important Target ◽  
Target Molecules

The nitrogen oxide (NO), a free radical molecule, plays a key role in the regulation of mammalian physiology and pathophysiology, e.g., in cardiovascular, nervous or immune systems. This molecule is produced from guanidino moiety of amino acid L-arginine with NG-hydroxy-L-arginine as intermediate and L-citrulline as a co-product of this reaction. This conversion is catalyzed by an ezyme called NO-synthase. The NO-synthase belongs to the cytochrome P450 superfamily and four its isoenzymes are known so far. Two (denoted NOS-I and III) are constitutive, generate lower amounts (pmol) of NO and are regulated by Ca++/calmodulin system. The others (NOS-II and IV) are inducible, produce a larger quantity of NO (nmol) and are regulated at a transcriptional level. The constitutive form is present, for example, in endothelial and neuronal cells whereas the inducible form is de novo synthesized as a consequence of certain stimuli (including cytokines) in macrophages, vascular smooth muscle cells and other cells. There are several target molecules for NO depending on cells. The most frequent target is supposed to be the soluble guanylate cyclase. However, superoxide anion is a very important target for NO, too. The reaction between these two molecules leads to the production of peroxynitrite, the fate of which depends on environmental conditions. Therefore, the importance of this reaction is still debated. This review deals with the nature of NO, the mechanisms of its production, the role of intermediate NG-hydroxy-L-arginine and summarizes the biology of superoxide anion with respect to its reaction with NO. A review with 218 references.

The role of nitric oxide in the regulation of the electrical activity of the trigeminal nerve in the rat

2021 ◽  
Author(s):  
S.O. Svitko ◽  
K.S. Koroleva ◽  
G.F. Sitdikova ◽  
K.A. Petrova
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Trigeminal Nerve ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
No Synthase ◽  
The Body ◽  
No Donor ◽  
No Signaling

Nitric oxide (NO) is a gaseous signaling molecule that regulates a number of physiological functions, including its role in the formation of migraine has been established. NO is endogenously produced in the body from L-arginine by NO synthase. The NO donor, nitroglycerin, is a trigger of migraine in humans and is widely used in the modeling of this disease in animals, which suggests the involvement of components of the NO signaling cascade in the pathogenesis of migraine. Based on the results obtained, it was found that an increase in the concentration of both the substrate for the synthesis of NO, L-arginine, and the NO donor, sodium nitroprusside, has a pro-nociceptive effect in the afferents of the trigeminal nerve. In this case, the effect of sodium nitroprusside is associated with the activation of intracellular soluble guanylate cyclase. Key words: nitric oxide, migraine, trigeminal nerve, L-arginine, guanylate cyclase, sodium nitroprusside, nociception.

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.

Nitric oxide inhibits neutrophil migration by a mechanism dependent on ICAM-1: Role of soluble guanylate cyclase

Nitric Oxide ◽  
2006 ◽  
Vol 15 (1) ◽  
pp. 77-86 ◽  
Author(s):  
Daniela Dal Secco ◽  
Ana P. Moreira ◽  
Andressa Freitas ◽  
João S. Silva ◽  
Marcos A. Rossi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Neutrophil Migration

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.

Capillary hydraulic conductivity is decreased by nitric oxide synthase inhibition

1995 ◽  
Vol 268 (5) ◽  
pp. H1856-H1861 ◽  
Author(s):  
R. E. Rumbaut ◽  
M. K. McKay ◽  
V. H. Huxley
Keyword(s):  
Nitric Oxide ◽  
Hydraulic Conductivity ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
No Synthase ◽  
Capillary Water ◽  
Cell Monolayers ◽  
Study Support ◽  
Oxide Synthase

Nitric oxide (NO) has been reported to modulate microvascular permeability to solutes in whole organs, venules, and cultured endothelial cell monolayers. NO derived from L-arginine via NO synthase activates soluble guanylate cyclase in vascular smooth muscle and endothelial cells. While the effects of NO on capillary water permeability have not been characterized, other activators of guanylate cyclase, such as sodium nitroprusside and atrial natriuretic peptide, increase capillary hydraulic conductivity (Lp). We hypothesized that inhibition of NO synthase with the arginine analogue, NG-monomethyl-L-arginine (L-NMMA), would decrease Lp from control levels. Lp was assessed in situ in single perfused frog mesenteric capillaries, first during control conditions (Lcontrolp) and then during superfusion (Ltestp) with either L-NMMA, NG-monomethyl-D-arginine (D-NMMA), a biologically inert enantiomer, or L-NMMA and L-arginine. Superfusion with 1 microM L-NMMA caused a decrease in Lp (Ltestp/Lcontrolp = 0.6 +/- 0.1, P < 0.001), whereas 1 microM D-NMMA was without effect on Lp (Ltestp/Lcontrolp = 1.0 +/- 0.2). The decrease in Lp by 1 microM L-NMMA was not only prevented by the presence of excess L-arginine (100 microM), but Lp increased from control (Ltestp/Lcontrolp = 1.4 +/- 0.2, P < 0.05). Furthermore, superfusion of L-arginine (100 microM) caused an increase in capillary Lp (Ltestp/Lcontrolp = 2.4 +/- 0.9, P < 0.05), whereas D-arginine had no effect on Lp (Ltestp/Lcontrolp = 1.2 +/- 0.3). The results of this study support our hypothesis that inhibition of NO synthase decreases capillary Lp in the intact circulation. In addition, L-arginine increases capillary Lp in our model.(ABSTRACT TRUNCATED AT 250 WORDS)

Is nitric oxide the final mediator regulating the migrating myoelectric complex cycle?

1995 ◽  
Vol 268 (2) ◽  
pp. G207-G214 ◽  
Author(s):  
A. Rodriguez-Membrilla ◽  
V. Martinez ◽  
M. Jimenez ◽  
E. Gonalons ◽  
P. Vergara
Keyword(s):  
Nitric Oxide ◽  
Small Intestine ◽  
Motor Pattern ◽  
No Synthase ◽  
Phase Iii ◽  
Motor Patterns ◽  
No Donor ◽  
Postprandial State ◽  
Synthase Inhibitor

The main objective was to study the role of nitric oxide (NO) in the conversion of migrating myoelectric complexes (MMC) to the irregular electrical activity characteristic of the postprandial state. Both rats and chickens were implanted with electrodes for electromyography in the small intestine. Intravenous infusion of NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, induced an organized MMC-like pattern in fed rats. Infusion of sodium nitroprusside, a NO donor, disrupted the MMC, inducing a postprandial-like motor pattern in fasting rats. Similarly, in chickens L-NNA mimicked the fasting pattern, consisting of a shortening of phase II, enlargement of phase III, orad displacement of the origin of the MMC, and an increase in the speed of phase III propagation. An inhibition of NO synthesis seems to be involved in the induction of the fasting motor pattern, whereas an increase of NO mediates the occurrence of the fed pattern. It is suggested that NO might be the final mediator in the control of small intestine motor patterns.

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 Nitric Oxide and the Neuroendocrine Control of the Osmotic Stress Response in Teleosts

2019 ◽  
Vol 20 (3) ◽  
pp. 489 ◽  
Author(s):  
Carla Cioni ◽  
Elisa Angiulli ◽  
Mattia Toni
Keyword(s):  
Nitric Oxide ◽  
Stress Response ◽  
Osmotic Stress ◽  
No Synthase ◽  
Hormone Release ◽  
Neurosecretory Neurons ◽  
Osmotic Stress Response ◽  
Osmotic Challenge ◽  
Osmotic Stimuli

The involvement of nitric oxide (NO) in the modulation of teleost osmoresponsive circuits is suggested by the facts that NO synthase enzymes are expressed in the neurosecretory systems and may be regulated by osmotic stimuli. The present paper is an overview on the research suggesting a role for NO in the central modulation of hormone release in the hypothalamo-neurohypophysial and the caudal neurosecretory systems of teleosts during the osmotic stress response. Active NOS enzymes are constitutively expressed by the magnocellular and parvocellular hypophysiotropic neurons and the caudal neurosecretory neurons of teleosts. Moreover, their expression may be regulated in response to the osmotic challenge. Available data suggests that the regulatory role of NO appeared early during vertebrate phylogeny and the neuroendocrine modulation by NO is conservative. Nonetheless, NO seems to have opposite effects in fish compared to mammals. Indeed, NO exerts excitatory effects on the electrical activity of the caudal neurosecretory neurons, influencing the amount of peptides released from the urophysis, while it inhibits hormone release from the magnocellular neurons in mammals.

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.

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