scholarly journals Nitric Oxide as a Central Molecule in Hypertension: Focus on the Vasorelaxant Activity of New Nitric Oxide Donors

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1041
Author(s):  
Gabriela Maria da Silva ◽  
Mirelly Cunha da Silva ◽  
Déborah Victória Gomes Nascimento ◽  
Ellen Mayara Lima Silva ◽  
Fabíola Furtado Fialho Gouvêa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Function ◽  
Cardiac Complications ◽  
Inhibition Of Proliferation ◽  
No Donors ◽  
Inflammatory Reactions ◽  
Great Relevance ◽  
Vasorelaxant Activity ◽  
And Migration

Cardiovascular diseases include all types of disorders related to the heart or blood vessels. High blood pressure is an important risk factor for cardiac complications and pathological disorders. An increase in circulating angiotensin-II is a potent stimulus for the expression of reactive oxygen species and pro-inflammatory cytokines that activate oxidative stress, perpetuating a deleterious effect in hypertension. Studies demonstrate the capacity of NO to prevent platelet or leukocyte activation and adhesion and inhibition of proliferation, as well as to modulate inflammatory or anti-inflammatory reactions and migration of vascular smooth muscle cells. However, in conditions of low availability of NO, such as during hypertension, these processes are impaired. Currently, there is great interest in the development of compounds capable of releasing NO in a modulated and stable way. Accordingly, compounds containing metal ions coupled to NO are being investigated and are widely recognized as having great relevance in the treatment of different diseases. Therefore, the exogenous administration of NO is an attractive and pharmacological alternative in the study and treatment of hypertension. The present review summarizes the role of nitric oxide in hypertension, focusing on the role of new NO donors, particularly the metal-based drugs and their protagonist activity in vascular function.

scholarly journals Role of NO in arterial vascular function of intertidal fish (Girella laevifrons) and marine fish (Isacia conceptionis)

2016 ◽  
Vol 76 (2) ◽  
pp. 500-505
Author(s):  
F. A. Moraga ◽  
N. Urriola-Urriola
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Marine Fish ◽  
Vascular Function ◽  
Isometric Tension ◽  
Mesenteric Arteries ◽  
Response Curves ◽  
Intertidal Fish ◽  
Branchial Arteries

Abstract Previous studies performed in intertidal fish (Girella laevifrons),as well as marine fish (Isacia conceptionis), showed that acetylcholine (ACh) produced contractions mediated by cyclooxygenases that were dependent on the area and potency of contraction in several arterial vessels. Given that the role of nitric oxide is poorly understood in fish, the objective of our study was to evaluate the role of nitric oxide in branchial afferent (ABA), branchial efferent (ABE), dorsal (DA) and mesenteric (MA) arterial vessels from both Girella laevifrons and Isacia conceptionis. We studied afferent and efferent branchial, dorsal and mesenteric arteries that were dissected from 6 juvenile specimens. Isometric tension studies were done using dose response curves (DRC) for Ach (10–13 to 10–3 M) and blockade with L-NAME (10–5 M), and DRC for sodium nitroprusside (SNP, a donor of NO). L-NAME produced an attenuation of the contractile response in the dorsal, afferent and efferent branchial arteries and a potentiation of the contraction in the MA. SNP caused 70% dilation in the mesenteric artery and 40% in the dorsal artery. Our results suggest that Ach promotes precarious dilatation in MA mediated by NO; data that is supported by the use of sodium nitroprusside. In contrast, in the vessels DA, ABA and EBA our results support that the pathway Ach-NO-relaxation is absent in both species.

Nitric Oxide and Immune Responses in Cancer: Searching for New Therapeutic Strategies

2021 ◽  
Vol 28 ◽  
Author(s):  
Adeleh Sahebnasagh ◽  
Fatemeh Saghafi ◽  
Sina Negintaji ◽  
Tingyan Hu ◽  
Mojtaba Shabani-Boroujeni ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Relevant Literature ◽  
Cochrane Library ◽  
Signaling Molecule ◽  
No Donors ◽  
The Cochrane Library ◽  
Oxide Synthase

: In recent years, there has been an increasing interest in understanding the mysterious functions of nitric oxide (NO) and how this pleiotropic signaling molecule contributes to tumorigenesis. This review attempts to expose and discuss the information available on the immunomodulatory role of NO in cancer and recent approaches to the role of NO donors in the area of immunotherapy. To address the goal, the following databases were searched to identify relevant literature concerning empirical evidence: The Cochrane Library, Pubmed, Medline, EMBASE from 1980 through March 2020. Valuable attempts have been made to develop distinctive NO-based cancer therapy. Although the data do not allow generalization, the evidence seems to indicate that low / moderate levels may favor tumorigenesis while higher levels would exert anti-tumor effects. In this sense, the use of NO donors could have an important therapeutic potential within immunotherapy, although there are still no clinical trials. The emerging understanding of NO-regulated immune responses in cancer may help unravel the recent features of this “double-edged sword” in cancer physiological and pathologic processes and its potential use as a therapeutic agent for cancer treatment. In short, in this review, we discuss the complex cellular mechanism in which NO, as a pleiotropic signaling molecule, participates in cancer pathophysiology. We also debate the dual role of NO in cancer and tumor progression, and clinical approaches for inducible nitric oxide synthase (iNOS) based therapy against cancer.

scholarly journals Nitric oxide and peroxynitrite trigger and enhance release of neutrophil extracellular traps

2019 ◽  
Vol 77 (15) ◽  
pp. 3059-3075 ◽  
Author(s):  
Aneta Manda-Handzlik ◽  
Weronika Bystrzycka ◽  
Adrianna Cieloch ◽  
Eliza Glodkowska-Mrowka ◽  
Ewa Jankowska-Steifer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Calcium Ionophore ◽  
Neutrophil Extracellular Traps ◽  
Calcium Ionophore A23187 ◽  
Human Neutrophils ◽  
Ionophore A23187 ◽  
Inflammatory Reactions ◽  
Extracellular Traps

Abstract Despite great interest, the mechanism of neutrophil extracellular traps (NETs) release is not fully understood and some aspects of this process, e.g. the role of reactive nitrogen species (RNS), still remain unclear. Therefore, our aim was to investigate the mechanisms underlying RNS-induced formation of NETs and contribution of RNS to NETs release triggered by various physiological and synthetic stimuli. The involvement of RNS in NETs formation was studied in primary human neutrophils and differentiated human promyelocytic leukemia cells (HL-60 cells). RNS (peroxynitrite and nitric oxide) efficiently induced NETs release and potentiated NETs-inducing properties of platelet activating factor and lipopolysaccharide. RNS-induced NETs formation was independent of autophagy and histone citrullination, but dependent on the activity of phosphoinositide 3-kinases (PI3K) and myeloperoxidase, as well as selective degradation of histones H2A and H2B by neutrophil elastase. Additionally, NADPH oxidase activity was required to release NETs upon stimulation with NO, as shown in NADPH-deficient neutrophils isolated from patients with chronic granulomatous disease. The role of RNS was further supported by increased RNS synthesis upon stimulation of NETs release with phorbol 12-myristate 13-acetate and calcium ionophore A23187. Scavenging or inhibition of RNS formation diminished NETs release triggered by these stimuli while scavenging of peroxynitrite inhibited NO-induced NETs formation. Our data suggest that RNS may act as mediators and inducers of NETs release. These processes are PI3K-dependent and ROS-dependent. Since inflammatory reactions are often accompanied by nitrosative stress and NETs formation, our studies shed a new light on possible mechanisms engaged in various immune-mediated conditions.

scholarly journals Senescence and Cancer: Role of Nitric Oxide (NO) in SASP

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1145
Author(s):  
Nesrine Mabrouk ◽  
Silvia Ghione ◽  
Véronique Laurens ◽  
Stéphanie Plenchette ◽  
Ali Bettaieb ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cancer Treatment ◽  
Cellular Senescence ◽  
Negative Effects ◽  
No Donors ◽  
Cell State ◽  
Age Related ◽  
A Cell ◽  
Secretory Phenotype

Cellular senescence is a cell state involved in both physiological and pathological processes such as age-related diseases and cancer. While the mechanism of senescence is now well known, its role in tumorigenesis still remains very controversial. The positive and negative effects of senescence on tumorigenesis depend largely on the diversity of the senescent phenotypes and, more precisely, on the senescence-associated secretory phenotype (SASP). In this review, we discuss the modulatory effect of nitric oxide (NO) in SASP and the possible benefits of the use of NO donors or iNOS inducers in combination with senotherapy in cancer treatment.

Regulation of metalloproteinases by nitric oxide in human trophoblast cells in culture

2001 ◽  
Vol 13 (6) ◽  
pp. 411 ◽  
Author(s):  
Virginia Novaro ◽  
Alejandro Colman-Lerner ◽  
Felipe Vadillo Ortega ◽  
Alicia Jawerbaum ◽  
Dante Paz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Embryo Implantation ◽  
No Production ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
No Donors ◽  
Multinucleated Cells ◽  
Nos Inhibitors ◽  
Spermine Nonoate

The process of embryo implantation requires extensive remodelling of the endometrial extracellular matrix, a function largely performed by matrix-degrading metalloproteinases (MMPs). In the present study, we used trophoblast cells isolated from human term placentas to study the regulation of MMPs by nitric oxide (NO). Using a combination of zymography, Western blot and indirect immunofluorescence, we showed that MMP-2 and MMP-9 are increased during the conversion from low-motile cytotrophoblast cells to the highly motile and differentiated syncytiotrophoblast multinucleated cells. We also observed an increase in NO production and NO synthase (NOS) expression during this cellular differentiation process. In addition, we demonstrated a positive regulatory role of NO on the activity and protein expression of MMP-2 and MMP-9, because NO donors (NOC-18 and spermine-NONOate) or the NOS substrate (L-arginine) stimulate, whereas NOS inhibitors (NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine) reduce the expression and gelatinolytic activity of MMP-2 and MMP-9 in isolated trophoblast cells. Taken together, these results suggest that, in differentiating trophoblasts, NO regulates the induction of matrix-degrading proteases required for invasion during embryo implantation.

scholarly journals The role of the endothelium in the hyperemic response to passive leg movement: looking beyond nitric oxide

2020 ◽  
Author(s):  
Joel D. Trinity ◽  
Oh Sung Kwon ◽  
Ryan M. Broxterman ◽  
Jayson R. Gifford ◽  
Andrew C. Kithas ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Vascular Function ◽  
No Synthase ◽  
Ketorolac Tromethamine ◽  
Arterial Infusion ◽  
Healthy Men ◽  
Leg Movement ◽  
Hyperemic Response

Passive leg movement (PLM) evokes a robust and predominantly nitric oxide (NO)-mediated increase in blood flow that declines with age and disease. Consequently, PLM is becoming increasingly accepted as a sensitive assessment of endothelium-mediated vascular function. However, a substantial PLM-induced hyperemic response is still evoked despite NO synthase (NOS) inhibition. Therefore, in 9 young healthy men (25±4 yrs), this investigation aimed to determine if the combination of two potent endothelium-dependent vasodilators, specifically prostaglandin (PG) and endothelium-derived hyperpolarizing factor (EDHF), account for the remaining hyperemic response to the two variants of PLM, PLM (60 movements) and single PLM (sPLM, 1 movement) when NOS is inhibited. The leg blood flow (LBF, Doppler ultrasound) response to PLM and sPLM following the intra-arterial infusion of NG-monomethyl L-arginine (L-NMMA), to inhibit NOS, was compared to the combined inhibition of NOS, cyclooxygenase (COX), and cytochrome P450 (CYP450) by L-NMMA, ketorolac tromethamine (KET), and fluconazole (FLUC), respectively. NOS inhibition attenuated the overall LBF (LBFAUC) response to both PLM (control: 456±194, L-NMMA: 168±127 ml, p<0.01) and sPLM (control: 185±171, L-NMMA: 62±31 ml, p=0.03). The combined inhibition of NOS, COX, and CYP450 (i.e. L-NMMA+KET+FLUC) did not further attenuate the hyperemic responses to PLM (LBFAUC: 271±97 ml, p>0.05) or sPLM (LBFAUC: 72±45 ml, p>0.05). Therefore, PG and EDHF do not collectively contribute to the non-NOS-derived NO-mediated, endothelium-dependent, hyperemic response to either PLM or sPLM in healthy young men. These findings add to the mounting evidence and understanding of the vasodilatory pathways assessed by the PLM and sPLM vascular function tests.

Restoring Oxygen Carrying Capacity of Sickle Erythrocytes with Nitric Oxide Donors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3785-3785
Author(s):  
Borys Hrinczenko
Keyword(s):  
Nitric Oxide ◽  
Oxygen Affinity ◽  
Red Cell ◽  
No Donors ◽  
Sickle Erythrocytes ◽  
Low Levels ◽  
Pre Treatment ◽  
Normal Controls

Abstract Sickle cell anemia (SCA) is an inherited blood disorder of hemoglobin function. A genetic mutation results in the substitution of a valine for glutamic acid residue at position 6 of the beta-globin chain yielding the mutant hemoglobin S (HbS). HbS polymerizes within erythrocytes during deoxygenation resulting in altered affinity of oxygen binding. The slightly different P50 (PO2 at which Hb is half-saturated with oxygen) values of sickle erythrocytes obtained during either oxygenation or deoxygenation (hysteresis) demonstrate HbS polymerization induced inhibition of oxygen affinity. Nitric oxide (NO) has been found to be an important signaling molecule in the circulatory system. NO derivatives of Hb provide insights into the physiological role of Hb. NO can bind to Hb at either the heme moiety forming nitrosylhemoglobin (HbNO) or to the conserved beta-93 cysteine yielding S-nitrosohemoglobin (SNO-Hb). In deoxygenated venous blood NO preferentially binds to the hemes of Hb forming HbNO while in oxygenated arterial blood NO binds to the beta-93 cysteine residues forming SNO-Hb. Increased oxygen affinity is seen in both SNO-Hb (Bonaventura C, et al, 1999) and also with HbNO. Decreasing the HbS P50 inhibits intra-erythrocyte HbS polymerization that may be an effective strategy to treat SCA. Clinical trials of NO breathing effects on oxygen affinity are conflicting. One study found an increased oxygen affinity of blood from SCA patients breathing 80 ppm NO with no effect seen in normal controls (Head A, et al, 1997). Another study found that levels of NO bound to Hb are too low to affect overall oxygen affinity (Gladwin M, et al, 1999). The purpose of this in vitro study was to determine the oxygen affinity of deoxygenated sickle erythrocytes pre-treated with exogenous NO donors. Blood from SCA (HbSS) and normal controls (HbAA) were collected and suspended in PBS buffer and deoxygenated with argon gas. The Hb concentration of each sample was calculated and then was either left untreated (control) or treated with varying concentrations of NO donors. The NO donors included: 2-(N, N-diethylamino)-diazenolate-2-oxide (DEANO), S-nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside (SNP), an aqueous solution of NO, and sodium trioxodinitrate (Angeli’s salt, AS). Methemoglobin and protein degradation were negligible. Samples were then transferred via airtight syringes into a stirred and temperature controlled (37°C) chamber of PBS solution at ambient oxygen pressure fitted with a very sensitive oxygen electrode. Oxygen levels were measured in real time. The amount of oxygen extracted from the PBS medium followed first order kinetics. Studies with HbSS red cell suspensions showed that the largest increment in oxygen extraction from the medium was obtained with DEANO pre-treatment. Calculations indicated that low levels of NO treatment, at approximately a 1:1000 ratio of [NO]/[heme], yielded the largest oxygen consumption. The effects of pre-treatment with the other NO donors on sickle erythrocytes (HbSS) were not as pronounced. DEANO is an NO donor yielding a “pure” NO radical as opposed to other redox forms. Similar studies with HbAA and HbSC did not show increases in oxygen extraction. Taken together the data suggest that low levels of NO perturb the quaternary structure of intraerythrocyte HbS polymer allowing depolymerization and increased oxygen affinity. The hope is that these in vitro studies will better characterize the role of NO in its interactions with Hb and the red cell and to use this knowledge for potential therapies in diseases such as SCA.

The role of nitric oxide synthase/nitric oxide in vascular smooth muscle control

Perfusion ◽  
2000 ◽  
Vol 15 (2) ◽  
pp. 97-104 ◽  
Author(s):  
D Bradford Sanders ◽  
Tara Kelley ◽  
Douglas Larson
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Nitric Oxide Synthase ◽  
Vascular Smooth Muscle ◽  
Vascular Function ◽  
No Production ◽  
Amyl Nitrite ◽  
Vascular Compliance ◽  
Oxide Synthase

Vascular compliance is dependent on endogenous and exogenous sources of nitric oxide (NO). In a discussion of therapeutics and NO derived via nitric oxide synthase (NOS) enzymes, it is necessary to examine the pathways of each drug to provide the clinical perfusionist with a greater understanding of the role of NOS/NO in vascular function. Endothelial-derived NO is a contributor in the vasoregulation of vascular smooth muscle. Therapeutics seek to mimic the vasodilatory effects of the endogenous NO. The therapeutics included in this review are nitroglycerin, nitroprusside, amyl nitrite, and inhalation of NO. L-Arginine supplementation provides additional substrate for the endogenous pathway that can augment NO production. NO is a small bioactive molecule involved in various biochemical pathways. Dysregulation of NO production can impair normal physiologic control of vascular compliance. Therefore, the purpose of this review is to provide the perfusionist with an understanding of the biochemical and pharmacological aspects of NOS/NO associated with vascular function.

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