Abstract 493: Renal Injury Induced by Nitric Oxide Depletion is Prevented by Concomitant Inhibition of Hydrogen Sulfide and/or Carbon Monoxide Production

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Sebastiaan Wesseling ◽  
Joost O Fledderus ◽  
Marianne C Verhaar ◽  
Jaap A Joles
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Carbon Monoxide ◽  
Renal Function ◽  
Hydrogen Sulfide ◽  
Renal Injury ◽  
Ischemia Reperfusion ◽  
No Synthase ◽  
Heme Oxygenase 1 ◽  
Plasma Urea

Chronic nitric oxide (NO) depletion induces hypertension and renal damage. Hydrogen sulfide (H 2 S) producing cystathionine-γ-lyase (CSE) and carbon monoxide (CO) producing heme oxygenase-1 (HO-1) appear to be protective in mechanically-induced renal injury (e.g. ischemia reperfusion). However, inhibition of CSE can reduce drug-induced renal injury (e.g. cisplatin). The role of renal H 2 S and HO-1 during chronic NO depletion is unknown. We hypothesized that renal injury secondary to NO depletion via inhibition of NO synthase is diminished by additional H 2 S depletion via inhibition of CSE. Rats (n=6/group) were treated with inhibitors of NO synthase (L-nitroarginine; LNNA), CSE (DL-propargylglycine; PAG), or HO-1 (Sn(IV) protoporphyrin IX dichloride; SnPP) for 1 or 4 weeks or with combinations (LNNA+PAG; LNNA+SnPP; PAG+SnPP or LNNA+PAG+SnPP) for 4 weeks. One week LNNA reduced urinary NOx excretion (35±2% vs baseline) and induced hypertension (173±12 vs. 137±3 mmHg; P<0.01) but renal function remained normal. Four weeks of LNNA further reduced NOx (7±1%), worsened hypertension (223±10 mmHg) and caused renal injury; plasma urea (17±4 vs 7±1 mmol/L; P<0.05), proteinuria (144±35 vs 17±2 mg/d; P<0.01). PAG or SnPP had no effect. NOx was reduced by PAG and increased by SnPP. Renal H 2 S production was completely blocked by PAG and enhanced by SnPP at 1 and 4 weeks. Renal HO-1 expression was induced by LNNA at 4 weeks and by PAG and SnPP at 1 and 4 weeks (all P<0.001). Adding PAG, SnPP, or both, to LNNA did not affect hypertension but preserved renal function. Combining PAG and SnPP had no effect on blood pressure or renal function. Reduction of urine NOx by LNNA was not affected by additional PAG (8±2%) but was ameliorated by adding SnPP (37±4%) or PAG+SnPP (42±9%). Renal H 2 S production was completely inhibited with all PAG-combinations (P<0.01), but was twofold enhanced by LNNA+SnPP (P<0.01). Renal HO-1 expression was increased by all combinations. NO depletion resulted in hypertension and progressive renal injury that was prevented by concomitant inhibition of CSE and/or HO-1. Depletion of H 2 S and CO in the absence of NO depletion had no effect on blood pressure and renal function. These data suggest that pathways from NO depletion to renal injury run via H 2 S or CO.

The role of nitric oxide in iron-induced rat renal injury

2004 ◽  
Vol 23 (11) ◽  
pp. 533-536 ◽  
Author(s):  
M Kadkhodaee ◽  
A Gol
Keyword(s):  
Nitric Oxide ◽  
Renal Function ◽  
Vitamin E ◽  
Renal Injury ◽  
Tissue Injury ◽  
Renal Tissue ◽  
No Synthase ◽  
Plasma Vitamin ◽  
Anti Oxidant ◽  
Plasma Vitamin E

Iron overload and enhanced hydroxyl radical (•OH) formation have been implicated as the causative factors of oxidative stress in different organs. Both pro-oxidant and anti-oxidant properties have been reported for nitric oxide (NO) in iron-mediated tissue injury. To determine the contribution of NO to iron-induced renal injury, eight groups of rats (eight in each group) were studied as follows: control (normal saline), L-Arg (L-arginine as a substrate of NO synthase, 400 mg/kg), L-NAME (an inhibitor of NO synthase, 8 mg/kg), Fe (iron dextran, 600 mg/kg), DFO (deferroxamine as a chelator of iron, 150 mg/kg), Fe+L-Arg, Fe+L-NAME, DFO+L-Arg. Twenty-four hours after the injections, blood samples were taken and kidneys removed for biochemical analysis. Plasma creatinine and urea were used to stimulate renal function. Renal tissue and plasma vitamin E levels, the most important endogenous fat soluble antioxidant, were measured by HPLC and UV detection. In this study, renal function was markedly reduced in the Fe group compared to controls (creatinine, 1.02± 0.05 mg/dL versus 0.78±0.04 P <0.05; urea, 49.59±1.69 mg/dL versus 40.75±0.86, P <0.01). Vitamin E levels were significantly lower in the Fe group compared to controls (plasma P <0.01; renal tissue P <0.05). Administration of L-Arg to Fe-treated groups prevented these reductions. L-NAME increased iron-induced toxicity significantly, demonstrated by further reduction in the vitamin E levels and renal function compared to the Fe group alone. We concluded that NO plays an important role in protecting the kidney from iron-induced nephrotoxicity. NO synthase blockade enhances iron-mediated renal toxicity in this model.

OP26 Renal injury induced by nitric oxide depletion is prevented by concomitant inhibition of hydrogen sulfide and/or carbon monoxide production

Nitric Oxide ◽  
2013 ◽  
Vol 31 ◽  
pp. S30-S31
Author(s):  
Sebastiaan Wesseling ◽  
Joost O. Fledderus ◽  
Marianne C. Verhaar ◽  
Jaap A. Joles
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Renal Injury

scholarly journals Medical Gases: A Novel Strategy for Attenuating Ischemia—Reperfusion Injury in Organ Transplantation?

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Arunotai Siriussawakul ◽  
Lucinda I. Chen ◽  
John D. Lang
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Organ Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inhaled Nitric Oxide ◽  
Clinical Consequence ◽  
Solid Organ

Ischemia reperfusion injury (IRI) is an inevitable clinical consequence in organ transplantation. It can lead to early graft nonfunction and contribute to acute and chronic graft rejection. Advanced molecular biology has revealed the highly complex nature of this phenomenon and few definitive therapies exist. This paper reviews factors involved in the pathophysiology of IRI and potential ways to attenuate it. In recent years, inhaled nitric oxide, carbon monoxide, and hydrogen sulfide have been increasingly explored as plausible novel medical gases that can attenuate IRI via multiple mechanisms, including microvascular vasorelaxation, reduced inflammation, and mitochondrial modulation. Here, we review recent advances in research utilizing inhaled nitric oxide, carbon monoxide, and hydrogen sulfide in animal and human studies of IRI and postulate on its future applications specific to solid organ transplantation.

scholarly journals Carbon Monoxide Being Hydrogen Sulfide and Nitric Oxide Molecular Sibling, as Endogenous and Exogenous Modulator of Oxidative Stress and Antioxidative Mechanisms in the Digestive System

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Edyta Korbut ◽  
Tomasz Brzozowski ◽  
Marcin Magierowski
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Heme Oxygenase ◽  
Gastric Mucosal Damage ◽  
Heme Oxygenase 1 ◽  
Enzymatic Antioxidants ◽  
Gi Tract ◽  
Liver And Pancreas

Oxidative stress reflects an imbalance between oxidants and antioxidants in favor of the oxidants capable of evoking tissue damage. Like hydrogen sulfide (H2S) and nitric oxide (NO), carbon monoxide (CO) is an endogenous gaseous mediator recently implicated in the physiology of the gastrointestinal (GI) tract. CO is produced in mammalian tissues as a byproduct of heme degradation catalyzed by the heme oxygenase (HO) enzymes. Among the three enzymatic isoforms, heme oxygenase-1 (HO-1) is induced under conditions of oxidative stress or tissue injury and plays a beneficial role in the mechanism of protection against inflammation, ischemia/reperfusion (I/R), and many other injuries. According to recently published data, increased endogenous CO production by inducible HO-1, its delivery by novel pharmacological CO-releasing agents, or even the direct inhalation of CO has been considered a promising alternative in future experimental and clinical therapies against various GI disorders. However, the exact mechanisms underlying behind these CO-mediated beneficial actions are not fully explained and experimental as well as clinical studies on the mechanism of CO-induced protection are awaited. For instance, in a variety of experimental models related to gastric mucosal damage, HO-1/CO pathway and CO-releasing agents seem to prevent gastric damage mainly by reduction of lipid peroxidation and/or increased level of enzymatic antioxidants, such as superoxide dismutase (SOD) or glutathione peroxidase (GPx). Many studies have also revealed that HO-1/CO can serve as a potential defensive pathway against oxidative stress observed in the liver and pancreas. Moreover, increased CO levels after treatment with CO donors have been reported to protect the gut against formation of acute GI lesions mainly by the regulation of reactive oxygen species (ROS) production and the antioxidative activity. In this review, we focused on the role of H2S and NO molecular sibling, CO/HO pathway, and therapeutic potential of CO-releasing pharmacological tools in the regulation of oxidative stress-induced damage within the GI tract with a special emphasis on the esophagus, stomach, and intestines and also two solid and important metabolic abdominal organs, the liver and pancreas.

Vasoactivity of the gasotransmitters hydrogen sulfide and carbon monoxide in the chicken ductus arteriosus

2011 ◽  
Vol 301 (4) ◽  
pp. R1186-R1198 ◽  
Author(s):  
Saskia van der Sterren ◽  
Pamela Kleikers ◽  
Luc J. I. Zimmermann ◽  
Eduardo Villamor
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Guanylate Cyclase ◽  
Vascular Tone ◽  
Soluble Guanylate Cyclase ◽  
Ductus Arteriosus ◽  
No Synthase ◽  
Mechanical Responses ◽  
Synthase Inhibitor

Besides nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) is a third gaseous messenger that may play a role in controlling vascular tone and has been proposed to serve as an O2 sensor. However, whether H2S is vasoactive in the ductus arteriosus (DA) has not yet been studied. We investigated, using wire myography, the mechanical responses induced by Na2S (1 μM–1 mM), which forms H2S and HS− in solution, and by authentic CO (0.1 μM-0.1 mM) in DA rings from 19-day chicken embryos. Na2S elicited a 100% relaxation (pD2 4.02) of 21% O2-contracted and a 50.3% relaxation of 62.5 mM KCl-contracted DA rings. Na2S-induced relaxation was not affected by presence of the NO synthase inhibitor l-NAME, the soluble guanylate cyclase (sGC) inhibitor ODQ, or the K+ channel inhibitors tetraethylammonium (TEA; nonselective), 4-aminopyridine (4-AP, KV), glibenclamide (KATP), iberiotoxin (BKCa), TRAM-34 (IKCa), and apamin (SKCa). CO also relaxed O2-contracted (60.8% relaxation) and KCl-contracted (18.6% relaxation) DA rings. CO-induced relaxation was impaired by ODQ, TEA, and 4-AP (but not by l-NAME, glibenclamide, iberiotoxin, TRAM-34 or apamin), suggesting the involvement of sGC and KV channel stimulation. The presence of inhibitors of H2S or CO synthesis as well as the H2S precursor l-cysteine or the CO precursor hemin did not significantly affect the response of the DA to changes in O2 tension. Endothelium-dependent and -independent relaxations were also unaffected. In conclusion, our results indicate that the gasotransmitters H2S and CO are vasoactive in the chicken DA but they do not suggest an important role for endogenous H2S or CO in the control of chicken ductal reactivity.

CHANGES OF NITRIC OXIDE SYNTHASE AND HYDROGEN SULFIDE IN BLOOD LYMPHOCYTES IN THE ACUTE PERIOD OF POLYTRAUMA

2019 ◽  
Vol 72 (8) ◽  
pp. 1473-1476
Author(s):  
Nataliya Matolinets ◽  
Helen Sklyarova ◽  
Eugene Sklyarov ◽  
Andrii Netliukh
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Tissue Injury ◽  
Traumatic Injury ◽  
Cell Types ◽  
No Synthase ◽  
Septic Complications ◽  
Acute Period ◽  
Gaseous Transmitters ◽  
The Moment

Introduction: Polytrauma patients have high risk of shock, septic complications and death during few years of follow-up. In recent years a lot of attention is paid to gaseous transmitters, among which are nitrogen oxide (NO) and hydrogen sulfide (H2S). It is known that the rise of NO and its metabolites levels occurs during the acute period of polytrauma. Nitric oxide and hydrogen sulfide are produced in different cell types, among which are lymphocytes. The aim: To investigate the levels of NO, NOS, iNOS, еNOS, H2S in lymphocytes lysate in patients at the moment of hospitalization and 24 hours after trauma. Materials and methods: We investigated the levels of NO, NO-synthase, inducible NO-synthase, endothelial NO-synthase, H2S in lymphocytes lysate in patients at the moment of hospitalization and 24 hours after trauma. Results: The study included 20 patients with polytrauma who were treated in the intensive care unit (ICU) of the Lviv Emergency Hospital. Tissue injury was associated with an increased production of NO, NOS, iNOS, еNOS during the acute period of polytrauma. At the same time, the level of H2S decreased by the end of the first day of traumatic injury. Conclusions: In acute period of polytrauma, significant increasing of iNOS and eNOS occurs with percentage prevalence of iNOS over eNOS on the background of H2S decreasing.

The Role of Reactive Oxygen Species, Kinases, Hydrogen Sulfide, and Nitric Oxide in the Regulation of Autophagy and Their Impact on Ischemia and Reperfusion Injury in the Heart

2020 ◽  
Vol 16 ◽  
Author(s):  
Andrey Krylatov ◽  
Leonid Maslov ◽  
Sergey Y. Tsibulnikov ◽  
Nikita Voronkov ◽  
Alla Boshchenko ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Hydrogen Sulfide ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Ischemia And Reperfusion ◽  
Oxygen Species ◽  
Ischemia And Reperfusion Injury ◽  
Adaptive Process

: There is considerable evidence in the heart that autophagy in cardiomyocytes is activated by hypoxia/reoxygenation (H/R) or in hearts by ischemia/reperfusion (I/R). Depending upon the experimental model and duration of ischemia, increases in autophagy in this setting maybe beneficial (cardioprotective) or deleterious (exacerbate I/R injury). Aside from the conundrum as to whether or not autophagy is an adaptive process, it is clearly regulated by a number of diverse molecules including reactive oxygen species (ROS), various kinases, hydrogen sulfide (H2S) and nitric oxide (NO). The purpose this review is to address briefly the controversy regarding the role of autophagy in this setting and to examine a variety of disparate molecules that are involved in its regulation.

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.

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