scholarly journals Involvement of tumor necrosis factor-α in natriuretic response to systemic infusion of nitric oxide synthase inhibitor in anesthetized mice

2010 ◽  
Vol 299 (1) ◽  
pp. F217-F224 ◽  
Author(s):  
Mohd Shahid ◽  
Joseph Francis ◽  
Khalid Matrougui ◽  
Dewan S. A. Majid
Keyword(s):  
Nitric Oxide ◽  
Kidney Tissue ◽  
No Synthase ◽  
Nitric Oxide Synthase Inhibitor ◽  
Renal Vasoconstriction ◽  
Tnf Α ◽  
Synthase Inhibitor ◽  
Factor Α ◽  
Oxide Synthase ◽  
Renal Responses

Systemic infusion of TNF-α exerts renal vasoconstriction but caused marked natriuresis in mice. Similar renal responses were also observed during systemic infusion of nitric oxide (NO) synthase inhibitors as opposed to their usual antinatriuretic responses when administered intrarenally. In the present study, we examined the hypothesis that acute NO blockade systemically induces TNF-α generation. which induces this natriuretic response. Renal responses to intravenous infusion of the NO synthase inhibitor nitro-l-arginine methyl ester (l-NAME; 0.2 μg·min−1·g body wt−1 for 85 min) and its impact on the plasma level of TNF-α were evaluated in anesthetized mice. Plasma TNF-α was undetected in untreated mice ( n = 7) but was elevated in l-NAME-treated mice (109 ± 22 pg/ml; P < 0.01 vs. untreated group; n = 7) along with an increase in TNF-α protein expression in kidney tissue. l-NAME infusion caused a usual increase in mean arterial pressure (MAP; 98 ± 3 to 122 ± 3 mmHg; P < 0.01) and decreases in renal blood flow (RBF; 8.6 ± 0.3 to 4.4 ± 0.2 ml·min−1·g−1; P < 0.01) and glomerular filtration rate (GFR; 1.14 ± 0.07 to 0.77 ± 0.04 ml·min−1·g−1; P < 0.01) with a marked increase in sodium excretion (UNaV; 0.48 ± 0.10 to 3.52 ± 0.85 μmol·min−1·g−1; P < 0.01). Interestingly, in mice ( n = 7) pretreated with the TNF-α blocker etanercept (5 mg/kg sc), the UNaV response to l-NAME infusion was markedly blunted (0.58 ± 0.08 to 1.22 ± 0.28 μmol·min−1·g−1; P = NS) although responses for MAP, RBF, and GFR were mostly unchanged. However, pretreatment with the superoxide scavenger tempol in mice ( n = 7) did not alter the UNaV response to l-NAME. These data demonstrate that l-NAME-induced natriuresis is mediated, at least in part, by concomitant generation of TNF-α during NO blockade.

Inhibition of nitric oxide synthase enhances superoxide activity in canine kidney

2004 ◽  
Vol 287 (1) ◽  
pp. R27-R32 ◽  
Author(s):  
Dewan S. A. Majid ◽  
Akira Nishiyama ◽  
Keith E. Jackson ◽  
Alexander Castillo
Keyword(s):  
Nitric Oxide ◽  
Protective Role ◽  
Potential Interaction ◽  
No Synthase ◽  
Anesthetized Dogs ◽  
Synthase Inhibitor ◽  
Qualitative Responses ◽  
Oxide Synthase ◽  
Renal Responses

To evaluate the role of a potential interaction between superoxide anion (O2−) and nitric oxide (NO) in regulating kidney function, we examined the renal responses to intra-arterial infusion of a superoxide dismutase mimetic, tempol (0.5 mg·kg−1·min−1), in anesthetized dogs treated with or without NO synthase inhibitor, Nω-nitro-l-arginine (NLA; 50 μg·kg−1·min−1). In one group of dogs ( n = 10), tempol infusion alone for 30 min before NLA infusion did not cause any significant changes in renal blood flow (RBF; 5.2 ± 0.4 to 5.0 ± 0.4 ml·min−1·g−1), glomerular filtration rate (GFR; 0.79 ± 0.04 to 0.77 ± 0.04 ml·min−1·g−1), urine flow (V; 13.6 ± 2.1 to 13.9 ± 2.5 μl·min−1·g−1), or sodium excretion (UNaV; 2.4 ± 0.3 to 2.2 ± 0.3 μmol·min−1·g−1). Interestingly, when tempol was infused in another group of dogs ( n = 12) pretreated with NLA, it caused increases in V (4.4 ± 0.4 to 9.7 ± 1.4 μl·min−1·g−1) and in UNaV (0.7 ± 0.1 to 1.3 ± 0.2 μmol·min−1·g−1) without affecting RBF or GFR. Although NO inhibition caused usual qualitative responses in both groups of dogs, the antidiuretic (47 ± 5 vs. 26 ± 4%) and antinatriuretic (67 ± 4 vs. 45 ± 11%) responses to NLA were seen much less in dogs pretreated with tempol. NLA infusion alone increased urinary excretion of 8-isoprostane (13.9 ± 2.7 to 22.8 ± 3.6 pg·min−1·g−1; n = 7), which returned to the control levels (11.6 ± 3.4 pg·min−1·g−1) during coadministration of tempol. These data suggest that NO synthase inhibition causes enhancement of endogenous O2− levels and support the hypothesis that NO plays a protective role against the actions of O2− in the kidney.

Role of Heparin and Nitric Oxide in the Cardiac and Regional Hemodynamic Properties of Protamine in Conscious Chronically Instrumented Dogs

2001 ◽  
Vol 94 (6) ◽  
pp. 1016-1025 ◽  
Author(s):  
Takeshi Oguchi ◽  
Marie-Françoise Doursout ◽  
Satoshi Kashimoto ◽  
Yang Yan Liang ◽  
Craig J. Hartley ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Vascular Resistance ◽  
Portal Blood Flow ◽  
Conscious Dogs ◽  
Nitric Oxide Synthase Inhibitor ◽  
Renal Vasoconstriction ◽  
Regional Hemodynamics ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Background Because protamine is administered to reverse heparin, a drug that might itself affect the pharmacologic properties of protamine, this study was designed to assess the properties of protamine alone and in the presence of heparin in conscious dogs. Methods Twelve dogs were instrumented to continuously record cardiac and regional hemodynamics. On separate occasions, a dose of protamine (0.5, 1, 3, 5, and 8 mg/kg) was randomly administered either alone or in the presence of heparin (ratio 100 IU/mg). Heparin (300 IU/kg) and protamine (3 mg/kg) were administered in the presence of N-methyl-L-arginine, a specific nitric oxide synthase inhibitor. Identical experiments were performed with protamine (8 mg/kg) in the absence of heparin on a separate occasion. Results Protamine alone produced limited cardiac and regional changes. In the presence of heparin, protamine produced hypotension at 3, 5, and 8 mg/kg, vasodilatation at 3 and 5 mg/kg, and a more pronounced dose-dependent increase in pulmonary pressure at 3, 5, and 8 mg/kg. Simultaneously, transient carotid vasodilatation at 3 and 5 mg/kg, coronary and hepatic vasodilatation at 3, 5, and 8 mg/kg, as well as a decrease in vertebral vascular resistance were recorded at 1, 3, and 8 mg/kg. Protamine produced an immediate increase followed by a secondary decrease in renal vascular resistance. Protamine-induced secondary pulmonary pressor effects were attenuated. In the presence of heparin, nitric oxide synthase blockade selectively attenuated protamine-induced immediate hypotension, systemic vasodilatation, and coronary, mesenteric, and hepatic vasodilations as well as the decrease in portal blood flow and accentuated the renal vasoconstriction. Conclusions The presence of heparin accentuated the decrease in cardiac function induced by protamine as well as its effects on regional circulation. The data provide evidence that the nitric oxide pathway is involved in the systemic and selective regional heparin-protamine-mediated vasodilatation in conscious dogs.

scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

Glomerular and tubular interactions between renal adrenergic activity and nitric oxide

1995 ◽  
Vol 268 (6) ◽  
pp. F1004-F1008 ◽  
Author(s):  
F. B. Gabbai ◽  
S. C. Thomson ◽  
O. Peterson ◽  
L. Wead ◽  
K. Malvey ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Glomerular Filtration ◽  
Renal Nerves ◽  
Ang Ii ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adrenergic Activity ◽  
Single Nephron ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Endothelium-dependent nitric oxide (EDNO) exerts control over the processes of glomerular filtration and tubular reabsorption. The importance of the renal nerves to the tonic influence of EDNO in the glomerular microcirculation and proximal tubule was tested by renal micropuncture in euvolemic adult male Munich-Wistar rats. The physical determinants of glomerular filtration and proximal reabsorption were assessed before and during administration of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in control animals and in animals 5–9 days after either ipsilateral surgical renal denervation (DNX) or after either sham surgery (SHX). L-NMMA caused single-nephron glomerular filtration rate to decline in control and SHX animals but not in DNX rats. L-NMMA caused a reduction in proximal reabsorption in control and SHX rats, which was prevented by prior DNX. DNX did not alter urinary guanosine 3',5'-cyclic monophosphate excretion, and, although DNX upregulates glomerular angiotensin II (ANG II) receptors, prior DNX did not alter intrarenal ANG II content as evaluated by radioimmunoassay. Some component of renal adrenergic activity is required for the full expression of the glomerular and tubular effects of blockade of nitric oxide synthase.

Effects of Early Neuronal and Delayed Inducible Nitric Oxide Synthase Blockade on Cardiovascular, Renal, and Hepatic Function in Ovine Sepsis

2010 ◽  
Vol 113 (6) ◽  
pp. 1376-1384 ◽  
Author(s):  
Matthias Lange ◽  
Atsumori Hamahata ◽  
Daniel L. Traber ◽  
Yoshimitsu Nakano ◽  
Aimalohi Esechie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Plasma Nitrite ◽  
Oxide Synthase ◽  
Organ Dysfunctions ◽  
Inducible Nitric Oxide

Background Recent evidence suggests that nitric oxide produced via the neuronal nitric oxide synthase is involved mainly in the early response to sepsis, whereas nitric oxide derived from the inducible nitric oxide synthase is responsible during the later phase. We hypothesized that early neuronal and delayed inducible nitric oxide synthase blockade attenuates multiple organ dysfunctions during sepsis. Methods Sheep were randomly allocated to sham-injured, nontreated animals (n = 6); injured (48 breaths of cotton smoke and instillation of Pseudomonas aeruginosa into the lungs), nontreated animals (n = 7); and injured animals treated with a neuronal nitric oxide synthase inhibitor from 1 to 12 h and an inducible nitric oxide synthase inhibitor from 12 to 24 h postinjury (n = 6). Results The injury induced arterial hypotension, vascular leakage, myocardial depression, and signs of renal and hepatic dysfunctions. The treatment significantly attenuated, but did not fully prevent, the decreases in mean arterial pressure and left ventricular stroke work index. Although the elevation of creatinine levels was partially prevented, the decreases in urine output and creatinine clearance were not affected. The injury-related increases in bilirubin levels, international normalized ratio, and lipid peroxidation in liver tissue were significantly attenuated. Although plasma nitrite/nitrate levels were significantly increased versus baseline from 12-24 h in controls, plasma nitrite/nitrate levels were not increased in treated animals. Conclusions The combination treatment shows potential benefit on sepsis-related arterial hypotension and surrogate parameters of organ dysfunctions in sheep. It may be crucial to identify the time course of expression and activation of different nitric oxide synthase isoforms in future investigations.

Myogenic reactivity is reduced in small renal arteries isolated from relaxin-treated rats

2002 ◽  
Vol 283 (2) ◽  
pp. R349-R355 ◽  
Author(s):  
Jacqueline Novak ◽  
Rolando J. J. Ramirez ◽  
Robin E. Gandley ◽  
O. David Sherwood ◽  
Kirk P. Conrad
Keyword(s):  
Nitric Oxide ◽  
Virgin Female ◽  
Renal Arteries ◽  
Mesenteric Arteries ◽  
Blood Levels ◽  
Renal Circulation ◽  
Nitric Oxide Synthase Inhibitor ◽  
Myogenic Responses ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Administration of the ovarian hormone relaxin to nonpregnant rats vasodilates the renal circulation comparable to pregnancy. This vasodilation is mediated by endothelin (ET), the ETB receptor, and nitric oxide. Furthermore, endogenous relaxin mediates the renal vasodilation and hyperfiltration that occur during gestation. The goal of this study was to investigate whether myogenic reactivity of small renal and mesenteric arteries is reduced in relaxin-treated rats comparable to the pregnant condition. Relaxin or vehicle was administered to virgin female Long-Evans rats for 5 days at 4 μg/h, thereby producing midgestational blood levels of the hormone. The myogenic responses of small renal arteries (200–300 μm in diameter) isolated from these animals were evaluated in an isobaric arteriograph system. Myogenic reactivity was significantly reduced in the small renal arteries from relaxin-treated compared with vehicle-treated rats. The reduced myogenic responses were mediated by the ETB receptor and nitric oxide since the selective ETB receptor antagonist RES-701–1 and the nitric oxide synthase inhibitor N G-nitro-l-arginine methyl ester restored myogenic reactivity to virgin levels. The influence of relaxin was not limited to the renal circulation because myogenic reactivity was also reduced in small mesenteric arteries isolated from relaxin-treated rats. Thus relaxin administration to nonpregnant rats mimics pregnancy, insofar as myogenic reactivity of small renal and mesenteric arteries is reduced in both conditions.

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