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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

      Submit here before September 30, 2024

      About Blood Purification: 3.0 Impact Factor I 5.6 CiteScore I 0.83 Scimago Journal & Country Rank (SJR)

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      Role of combined L-arginine and prostaglandin E1 in renal ischemia-reperfusion injury.

      Nephron. Physiology
      Alprostadil, pharmacology, Animals, Arginine, Creatinine, blood, Disease Models, Animal, Drug Therapy, Combination, Kidney, drug effects, pathology, physiology, Kidney Diseases, drug therapy, Male, Rats, Rats, Sprague-Dawley, Reperfusion Injury, Sodium, urine, Survival Analysis, Urine, Vasodilator Agents

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          Abstract

          L-Arginine (L-arg) and Prostaglandin E(1) (PGE(1)) have been used effectively as single agents to ameliorate renal ischemia-reperfusion injury. We hypothesized that combined treatment with L-arg and PGE(1 )would be more effective. The left renal artery of male Sprague-Dawley rats was clamped for 45 min and the right kidney was removed. Fifty six rats were randomly allocated into 5 groups each consisted of 12 rats except sham group (n = 8). (1) sham, underwent right nephrectomy only; (2) control, untreated ischemic rats; (3) L-arg group, L-arg-treated ischemic rats; (4) PGE(1) group, PGE(1)-treated ischemic rats; (5) L-arg+PGE(1) group, ischemic rats treated with both L-arg and PGE(1). Renal function and histology were assessed on days 2 and 7 postoperatively. All rats, except control ones, showed a significant improvement of renal function towards normal on postoperative day 7. Serum creatinine and creatinine clearance were significantly better in L-arg+PGE(1) group compared to all other groups on day 7. With the exception of sham-operated and L-arg+PGE(1)-treated animals, all other groups showed significant increases in fractional excretion of sodium (FE(Na)) in response to renal ischemia-reperfusion. The severest tubular damage was determined in the kidneys of control rats. Rats treated with L-arg+PGE(1) had the least severe tubular damage. The administration of either L-arg or PGE(1) attenuates both functional and structural consequences of renal warm ischemia. A near total protection might be achieved when both agents are administered concomitantly. Copyright 2007 S. Karger AG, Basel.

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          Most cited references29

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          Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines.

          To test the hypothesis that nitric oxide (NO) limits endothelial activation, we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 (VCAM-1). In a concentration-dependent manner, NO inhibited interleukin (IL)-1 alpha-stimulated VCAM-1 expression by 35-55% as determined by cell surface enzyme immunoassays and flow cytometry. This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays, was unaffected by cGMP analogues, and was quantitatively similar after stimulation by either IL-1 alpha, IL-1 beta, IL-4, tumor necrosis factor (TNF alpha), or bacterial lipopolysaccharide. NO also decreased the endothelial expression of other leukocyte adhesion molecules (E-selectin and to a lesser extent, intercellular adhesion molecule-1) and secretable cytokines (IL-6 and IL-8). Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1, but did not augment cytokine-induced VCAM-1 expression. Nuclear run-on assays, transfection studies using various VCAM-1 promoter reporter gene constructs, and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription, in part, by inhibiting NF-kappa B. We propose that NO's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall.
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            Nitric oxide: an endogenous modulator of leukocyte adhesion.

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              An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation.

              Microsomes prepared from rabbit or pig aortas transformed endoperoxides (PGG2 or PGH2) to an unstable substance (PGX) that inhibited human platelet aggregation. PGX was 30 times more potent in this respect than prostaglandin E1. PGX contracted some gastrointestinal smooth muscle and relaxed certain isolated blood vessels. Prostaglandin endoperoxides cause platelet aggregation possibly through the generation by platelets of thromboxane A2. Generation of PGX by vessel walls could be the biochemical mechanism underlying their unique ability to resist platelet adhesion. A balance between formation of anti- and pro-aggregatory substances by enzymes could also contribute to the maintenance of the integrity of vascular endothelium and explain the mechanism of formation of intra-arterial thrombi in certain physiopathological conditions.
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