Regulatory interactions between inducible nitric oxide synthase and eicosanoids in glomerular immune injury
| Autor: | Elias A. Lianos, Kelly Guglielmi, Mukut Sharma |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Male
Leukotriene B4 Kidney Glomerulus Gene Expression Nitric Oxide Synthase Type II Basement Membrane Rats Sprague-Dawley Thromboxane A2 chemistry.chemical_compound immune injury in glomerulus 0302 clinical medicine Enzyme Inhibitors 0303 health sciences biology antiinflammatory strategies Glomerulonephritis 3. Good health Nitric oxide synthase Nephrology 030220 oncology & carcinogenesis Enzyme Induction Arachidonic acid lipids (amino acids peptides and proteins) medicine.medical_specialty Nitric oxide 03 medical and health sciences nitric oxide Internal medicine medicine Animals Humans Cyclooxygenase Inhibitors RNA Messenger Nitrites 030304 developmental biology DNA Primers Nitrates Base Sequence Lysine inducible nitric oxide synthase medicine.disease Rats Disease Models Animal Endocrinology Eicosanoid chemistry biology.protein Eicosanoids eicosanoids in glomerular injury Immunization Cyclooxygenase Nitric Oxide Synthase glomerulonephritis |
| Zdroj: | Kidney International. (3):645-653 |
| ISSN: | 0085-2538 |
| DOI: | 10.1046/j.1523-1755.1998.00791.x |
| Popis: | Regulatory interactions between inducible nitric oxide synthase and eicosanoids in glomerular immune injury. In a rat model of glomerular immune injury induced by administration of anti-glomerular basement membrane antibody and resembling human rapidly progressive glomerulonephritis, we explored whether activation of inducible nitric oxide synthase (iNOS) regulates synthesis of eicosanoids originating from cyclooxygenation or lipoxygenation of arachidonic acid. At early stages (24 hr) of injury, inhibition of iNOS using the selective inhibitor L-N6-(1-iminoethyl) lysine (L-NIL) at doses sufficient to reduce urinary excretion of nitrate/nitrite, reduced glomerular synthesis of the prostaglandins PGE2 and PGI2, but had no effect on that of thromboxane A2 (TxA2). The syntheses of 5-hydroxyeicosatetraenoic acid (HETE), 15-HETE and leukotriene B4 (LTB4) were also reduced. That of 12-HETE remained unchanged. We also explored the effect of arachidonate cyclooxygenation and lipoxygenation eicosanoids on iNOS expression. Administration of the cyclooxygenase (COX) inhibitor, indomethacin, at doses sufficient to inhibit glomerular prostaglandin synthesis, increased iNOS mRNA levels in glomeruli. Administration of the 5-lipoxygenase (5-LO) inhibitor, MK-0591, at doses sufficient to inhibit glomerular LTB4 synthesis also increased iNOS mRNA. The effect of 5-LO inhibition on iNOS expression was more pronounced than that of COX inhibition. In nephritic animals given the iNOS inhibitor, L-NIL, or indomethacin proteinuria worsened. In those given the 5-lipoxygenase inhibitor there was no change in urine protein excretion. These observations point to regulatory interactions between the arachidonic acid and the L-arginine:NO pathways in glomerulonephritis. These interactions are of importance in considering antiinflammatory strategies based on inhibition of iNOS or of specific eicosanoids. |
| Databáze: | OpenAIRE |
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