NITROGEN OXIDE ROLE IN MANIFESTATION OF RESPIRATORY EFFECTS OF INCREASED EXOGENOUS IL-1Β LEVEL IN BLOOD-VASCULAR SYSTEM

2019 ◽  
pp. 91-102
Author(s):  
A.A. Klinnikova ◽  
G.A. Danilova ◽  
N.P. Aleksandrova
Keyword(s):  
Nitric Oxide ◽  
Intravenous Administration ◽  
Inflammatory Cytokine ◽  
Vascular System ◽  
Specific Inhibitor ◽  
External Respiration ◽  
Respiratory Effects ◽  
Before And After ◽  
Keywords Cytokines ◽  
Ventilation Response

The purpose of the study is to identify the role of nitrergic mechanisms in the ability of the pro-inflammatory cytokine IL-1β to influence the respiration pattern and hypoxic ventilation response. Materials and Methods. The experiments were performed on 42 anesthetized rats. To conduct an inhibitory analysis of the nitric oxide role in the manifestation of IL-1β respiratory effects, the authors used a non-selective inhibitor of NO-synthases of Nitro-L-arginine-methyl ether (L-NAME), and a highly specific inhibitor of inducible nitric oxide synthase, aminoguanidine bicarbonate. The hypoxic ventilation response was evaluated by a rebreathing method with a hypoxic gas mixture before and after intravenous administration of human recombinant IL-1β. Pneumatic tachometry was used to register the parameters of external respiration. Results. Intravenous administration of IL-1β has an activating effect on respiration and causes an increase in tidal volume by 36±5.2 %, minute respiration volume by 23±3.8 % and average inspiratory flow rate by 20±3.0 %. However, an increase in IL-1β systemic level decreases the ventilation response to hypoxia. Inhibition of NO-synthase activity with both L-NAME and aminoguanidine reduces IL-1β respiratory effects. Conclusion. One of the mechanisms to implement the respiratory effects of the key pro-inflammatory cytokine IL-1β in case of increase in its circulating level is an increase in the synthesis of nitric oxide with vascular endothelium cells. Keywords: cytokines, interleukin-1β, ventilation, ventilation response to hypoxia, hypoxic chemoreflex, nitric oxide. Цель исследования. Выявление роли нитрергических механизмов в способности провоспалительного цитокина ИЛ-1β оказывать влияние на паттерн дыхания и гипоксический вентиляционный ответ. Материалы и методы. Эксперименты выполнены на 42 наркотизированных крысах. Для проведения ингибиторного анализа роли оксида азота в проявлении респираторных эффектов ИЛ-1β использовались неселективный ингибитор NO-синтаз L-нитро-аргинин-метилэфира (L-NAME), а также высокоспецифичный ингибитор индуцибельной синтазы оксида азота аминогуанидина бикарбоната. Гипоксический вентиляционный ответ оценивался методом возвратного дыхания гипоксической газовой смесью до и после внутривенного введения человеческого рекомбинантного ИЛ-1β. Для регистрации параметров внешнего дыхания использовался метод пневмотахометрии. Результаты. Показано, что внутривенное введение ИЛ-1β оказывает активирующее влияние на дыхание, вызывая увеличение дыхательного объема на 36,0±5,2 %, минутного объема дыхания – на 23,0±3,8 % и средней скорости инспираторного потока – на 20,0±3,0 %. Вместе с тем повышение системного уровня ИЛ-1β вызывает ослабление вентиляционного ответа на гипоксию. Ингибирование NO-синтазной активности с помощью как L-NAME, так и аминогуанидина ослабляет респираторные эффекты ИЛ-1β. Выводы. Одним из механизмов реализации респираторных эффектов ключевого провоспалительного цитокина ИЛ-1β при повышении его циркулирующего уровня является усиление синтеза оксида азота клетками сосудистого эндотелия. Ключевые слова: цитокины, интерлейкин-1β, вентиляция, вентиляционный ответ на гипоксию, гипоксический хеморефлекс, оксид азота.

Hypotensive effect of ANG II and ANG-(1–7) at the caudal ventrolateral medulla involves different mechanisms

2002 ◽  
Vol 283 (5) ◽  
pp. R1187-R1195 ◽  
Author(s):  
A. C. Alzamora ◽  
R. A. S. Santos ◽  
M. J. Campagnole-Santos
Keyword(s):  
Nitric Oxide ◽  
Arterial Pressure ◽  
Specific Inhibitor ◽  
Hypotensive Effect ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Caudal Ventrolateral Medulla ◽  
Before And After ◽  
Male Wistar Rats ◽  
Vascular Tonus

The objective of the present study was to determine the contribution of the autonomic nervous system and nitric oxide to the depressor effect produced by unilateral microinjection of ANG-(1–7) and ANG II into the caudal ventrolateral medulla (CVLM). Unilateral microinjection of ANG-(1–7), ANG II (40 pmol), or saline (100 nl) was made into the CVLM of male Wistar rats anesthetized with urethane before and after intravenous injection of 1) methyl-atropine, 2.5 mg/kg; 2) prazosin, 25 μg/kg; 3) the nitric oxide synthase (NOS) inhibitor, N G-nitro-l-arginine methyl ester (l-NAME), 5 mg/kg; or 4) the specific inhibitor of neuronal NOS, 7-nitroindazole (7-NI), 45 mg/kg. Arterial pressure and heart rate (HR) were continuously monitored. Microinjection of ANG-(1–7) or ANG II into the CVLM produced a significant decrease in mean arterial pressure (MAP; −11 ± 1 mmHg, n = 12 and −10 ± 1 mmHg, n= 10, respectively) that was not accompanied by consistent changes in HR or in cardiac output. The effect of ANG-(1–7) was abolished after treatment with methyl-atropine (−3 ± 0.6 mmHg, n = 9) or l-NAME (−2.3 ± 0.5 mmHg, n = 8) or 7-NI (−2.8 ± 0.6 mmHg, n = 5). In contrast, these treatments did not significantly interfere with the ANG II effect (−10 ± 2.6 mmHg, n = 8; −8 ± 1.5 mmHg, n = 8; and −12 ± 3.6 mmHg, n = 6; respectively). Peripheral treatment with prazosin abolished the hypotensive effect of ANG-(1–7) and ANG II. Microinjection of saline did not produce any significant change in MAP or in HR. These results suggest that the hypotensive effect produced by ANG II at the CVLM depends on changes in adrenergic vascular tonus and, more importantly, the hypotensive effect produced by ANG-(1–7) also involves a nitric oxide-related mechanism.

The role of neuronal NO synthase in the respiratory effects of TNF-α

2021 ◽  
Author(s):  
A.A. Klinnikova ◽  
G.A. Danilova ◽  
N.P. Aleksandrova
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Ventilatory Response ◽  
Neuronal Nitric Oxide Synthase ◽  
Key Words Cytokines ◽  
Respiratory Effects ◽  
Tnf Α ◽  
Before And After ◽  
Factor Α ◽  
Oxide Synthase

It was shown that an increase level of proinflammatory cytokines has a modulating effect on the reflex control of respiration. The aim of this study was to investigate the involvement of neuronal nitric oxide synthase (nNOS) in the mechanisms of the influence of an increased level of Tumor necrosis factor – α (TNF-α) on the hypoxic ventilatory response. To achieve this goal, experiments were carried out on urethane anesthetized rats with intravenous administration of TNF-α before and after pretreatment with 7-nitroindazole specific nNOS inhibitor. The hypoxic ventilation response was assessed by rebreathing with a hypoxic gas mixture before and after administration of TNF-α. We found that TNF-α decreased the ventilatory response to hypoxia. Pretreatment with nNOS inhibitor reduced respiratory effects of TNF-α. Key words: cytokines, TNF-α, hypoxia, chemoreflex, respiration, ventilation, neuronal nitric oxide synthase.

Nitric oxide modulates arterial baroreflex control of heart rate in conscious lambs in an age-dependent manner

2001 ◽  
Vol 280 (5) ◽  
pp. H2255-H2263 ◽  
Author(s):  
Alp Sener ◽  
Francine G. Smith
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Intravenous Administration ◽  
Systolic Arterial Pressure ◽  
Dependent Manner ◽  
Arterial Baroreflex ◽  
Baroreflex Control ◽  
Postnatal Maturation ◽  
Age Dependent ◽  
Before And After

Experiments were carried out in conscious chronically instrumented lambs aged 1 ( n = 6) and 6 wk ( n = 5) to evaluate the arterial baroreflex control of heart rate (HR) during postnatal maturation and to investigate any modulatory role of endogenously produced nitric oxide (NO). Before and after intravenous administration of 20 mg/kg of the l-arginine analog N G-nitro-l-arginine methyl ester (l-NAME), the arterial baroreflex was assessed by measuring HR responses to increases and decreases in systolic arterial pressure achieved by intravenous administration of phenylephrine and sodium nitroprusside. The HR range over which the baroreflex operates and minimum HR as well as maximum gain were greater at 1 than at 6 wk of age. These age differences were abolished in the presence ofl-NAME, which decreased the HR range and gain of the arterial baroreflex control of HR at 1 but not at 6 wk of age. These data provide new information that age-dependent effects of the arterial baroreflex appear to result from effects of endogenously produced NO.

Effects of acute nitric oxide inhibition on rat glomerular microcirculation

1991 ◽  
Vol 261 (2) ◽  
pp. F360-F363 ◽  
Author(s):  
R. Zatz ◽  
G. de Nucci
Keyword(s):  
Nitric Oxide ◽  
Specific Inhibitor ◽  
Systemic Hypertension ◽  
Hydraulic Pressure ◽  
Acute Administration ◽  
Before And After ◽  
Single Nephron ◽  
Glomerular Ultrafiltration ◽  
Glomerular Hemodynamics ◽  
Relaxing Effect

Endothelium-derived relaxing factor (EDRF), recently identified as nitric oxide (NO), has been shown to be released by glomerular endothelial cells and might influence the glomerular microcirculation. To examine this hypothesis, we studied in rats the renal effect of acute administration of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthesis. Adult male Munich-Wistar rats were studied before and after intravenous administration of either pure saline or a bolus injection of L-NMMA (20 mg) followed by a continuous infusion of the inhibitor (0.4 mg/min). Although saline alone had no effect on systemic or glomerular hemodynamics, L-NMMA promoted marked systemic hypertension, glomerular arteriolar vasoconstriction, and glomerular hypoperfusion. Since efferent resistance was disproportionately increased, glomerular hydraulic pressure was also markedly elevated. The glomerular ultrafiltration coefficient (Kf) fell to 42% of control. Single-nephron glomerular filtration rate was unaffected. Striking polyuria was also observed. These findings suggest that EDRF exerts a basal relaxing effect on the glomerular microcirculation.

scholarly journals Role of endogenous nitric oxide on PAF-induced vascular and respiratory effects

1995 ◽  
Vol 4 (2) ◽  
pp. 124-129 ◽  
Author(s):  
M. Clement ◽  
M. Albertini
Keyword(s):  
Nitric Oxide ◽  
Cardiac Activity ◽  
Hypotensive Effect ◽  
Synthesis Inhibitor ◽  
Mechanically Ventilated ◽  
Respiratory Effects ◽  
Basal Tone ◽  
Before And After ◽  
Endogenous Nitric Oxide

The role of endogenous nitric oxide (NO) on vascular and respiratory smooth muscle basal tone was evaluated in six anaesthetized, paralysed, mechanically ventilated pigs. The involvement of endogenous NO in PAF-induced shock and airway hyperresponsiveness was also studied. PAF (50 ng/kg, i.v.) was administered before and after pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v.), an NO synthesis inhibitor. PAF was also administered to three of these pigs after indomethacin infusion (3 mg/kg, i.v.). In normal pigs, L-NAME increased systemic and pulmonary vascular resistances, caused pulmonary hypertension and reduced cardiac output and stroke volume. The pulmonary vascular responses were correlated with the increase in static and dynamic lung elastances, without changing lung resistance. Inhibition of NO synthesis enhanced the PAF-dependent increase in total, intrinsic and viscoelastic lung resistances, without affecting lung elastances or cardiac activity. The systemic hypotensive effect of PAF was not abolished by pretreatment with L-NAME or indomethacin. This indicates that systemic hypotension is not correlated with the release of endogenous NO or prostacyclines. Indomethacin completely abolished the PAF-dependent respiratory effects.

scholarly journals CYCLOOXYGENASE MECHANISMS IN THE REGULATION OF RESPIRATORY EFFECTS OF TUMOR NECROSIS FACTOR

2019 ◽  
Vol 19 (1S) ◽  
pp. 17-17
Author(s):  
G A Danilova ◽  
A A Klinnikova ◽  
N P Aleksandrova
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Inflammatory Cytokine ◽  
Ventilatory Response ◽  
Hypoxic Ventilatory Response ◽  
Respiratory Effects ◽  
Cox Inhibitor ◽  
Tnf Α ◽  
Before And After ◽  
Necrosis Factor

Introduction. It is known that the systemic level of the major pro-inflammatory cytokine increases in many respiratory diseases such as asthma, COPD and sleep apnea [1, 2]. The lung ventilation changes and the pathological types of breathing are typical in these diseases. By the reason, the research of the respiratory effects of cytokine is actual. The aim of this study was to compare the respiratory effects of tumor necrosis factor - α (TNF-α) before and after pretreatment with diclofenac, a nonspecific cyclooxygenase (COX) inhibitor. Materials and methods. Тhe experiments were performed in tracheostomized anaesthetized with urethane rats. A respiratory flow head connected to a pneumotachometer (AD Instruments ML141 Spirometer, Dunedin, New Zealand) was used to measure peak airflow and respiratory rate. The hypoxic ventilatory response was measured by using rebreathing with hypoxic gas mixture before and after the tail vein injection of TNF-α (10 μg/rat). In order to determine the role of the cyclooxygenase pathway in the ventilatory effects of TNF-α, introperitoneal administration of diclofenac, a nonspecific COX inhibitor, was used (0.5 mg/rat). Results and discussion. We have shown that the increase in level of TNF-α in blood increased the parameters of respiration such as minute ventilation (by 40%), tidal volume (by 18%), and the mean inspiratory flow (by 33%). The slope of the hypoxic ventilatory response decreased from 6.06 ± 0.91 to 3.48 ± 0.38 ml/min-1 mmHg-1 (by 40%) 40 min after administration of TNF-α (p < 0.05), the slope of tidal volume and mean inspiratory flow also decreased (by 27%) (p < 0.05). After pretreatment with diclofenac, the influence of TNF-α on breathing was dampened, as no significant changes were observed. Conclusion. We concluded that the elevation of inflammatory cytokine level in blood intensifies ventilation during the resting breathing that may be associated with increased central inspiratory activity. At the same time TNF-α reduces the chemoreflex sensitivity to hypoxia, thereby worsening the compensatory capabilities of the respiratory system. Thus, the results of our study suggest participation of inflammatory cytokines in mechanisms of central breathing control and chemoreception. Diclofenac pretreatment eliminated the respiratory effects of TNF-α. The data indicate that the ability of TNF-α to enhance basal ventilation and to reduce the ventilatory hypoxic response is mediated by the COX pathway.

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.

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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