scholarly journals Gastroprotective Efficacy of Coenzyme Q10 in Indomethacin-Induced Gastropathy: Other Potential Mechanisms

Ulcers ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Asmaa M. Malash ◽  
Dalaal M. Abdallah ◽  
Azza M. Agha ◽  
Sanna A. Kenawy
Keyword(s):  
Nitric Oxide ◽  
Acid Output ◽  
Titratable Acidity ◽  
Gastric Volume ◽  
Gastric Ulceration ◽  
Ulcer Formation ◽  
Current Investigation ◽  
Peptic Activity ◽  
Nitric Oxide Synthase Inhibitor ◽  
Dose Levels

Though recently the mitochondrial bioenergetic coenzyme (Co)Q10 has been shown to protect against indomethacin-induced gastric ulceration, yet the full mechanistic cassettes have not been investigated. Therefore, the current investigation assessed further gastroprotective mechanisms of CoQ10 using the indomethacin-induced gastropathy model. While CoQ10 was administered at 3 dose levels to male Wistar rats, the proton pump inhibitor, pantoprazole, was given at 4 dose levels ahead of pyloric ligation and indomethacin administration. Indomethacin evoked gastric ulcerations that were associated by decreased gastric mucosal nitric oxide and glutathione levels. The NSAID reduced gastric volume and mucin content, but increased titratable acidity, acid output, and peptic activity. CoQ10, especially at the higher dose levels, as well as pantoprazole pretreatments reverted almost all diversions induced by the NSAID to different extends. Moreover, preadministration with the nonselective nitric oxide synthase inhibitor, L-NAME, boosted ulcer formation that was associated by suppression of gastric mucosal nitric oxide in CoQ10 and pantoprazole-treated groups. The current investigation shows that CoQ10 guards against gastric ulceration via its partial inhibition of titratable acidity and peptic activity, as well as enhancement of mucin secretion due to both gastric mucosal nitric oxide and glutathione replenishment, especially at the higher dose levels.

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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