l -Arginine Treatment Alters the Kinetics of Nitric Oxide and Superoxide Release and Reduces Ischemia/Reperfusion Injury in Skeletal Muscle

Abstract

L-Arginine treatment decreased superoxide generation by cNOS while increasing NO accumulation, leading to protection from constriction (microvessel area, 17.77+/-0.95 versus 11.66+/-2.21 microm2 untreated, P<.0005) and reduction of edema after reperfusion (interfiber area, 16.56+/-2.13% versus 27.68+/-7.70% untreated, P<.005).

Race-Specific Differences in Endothelial Function

“…Recently, evidence has accumulated that O 2 Ϫ production and its interaction with NO, yielding the strong oxidant ONOO Ϫ , play central roles in vascular pathophysiology. 6 The present study demonstrates race-specific differences in endothelial NO bioavailability and ONOO Ϫ formation. These differences arise because endothelial cells from blacks generate significantly more O 2 Ϫ , primarily from 2 enzymatic sources: NAD(P)H-oxidase and eNOS.…”

“…Compared with whites, the steady state of NO/O 2 Ϫ /ONOO Ϫ balance in the endo- thelial cells from blacks is kept closer to the redox state that had been documented in the endothelium-impaired function disorders. 3,6,15,23 …”

“…In the majority of cases, the source of O 2 Ϫ excess is uncertain, although involvement of NAD(P)H-dependent oxidases, xanthine oxidase, cyclooxygenase, mitochondrial oxidases, and endothelial nitric oxide synthase (eNOS) and neuronal NOS have been suggested. [3][4][5][6] It should be noted that the net effect of the reaction between NO and O 2 Ϫ compromises reduction of concentration of both substrates as well as biological effects of ONOO Ϫ itself. Peroxynitrite induces the oxidation of proteins, DNA, and lipids in vascular walls.…”

Localization of Inducible Nitric Oxide Synthase to Mast Cells During Ischemia/Reperfusion Injury of Skeletal Muscle

“…Loss of NOS III activity, caused by either loss or inactivation of NOS III protein, would be expected to result in vasoconstriction, neutrophil extravasation, and edema, which could contribute to cell death by extending the episode of ischemia through the "no-reflow" phenomenon (Ames et al, 1968;Kanwar and Kubes, 1995;Kubes, 1993;Menger et al 1997). Pharmacological treatments that increase NO levels early during reperfusion or ischemic pre-conditioning (which is in part NOS III-mediated), protect skeletal muscle from IRmediated constriction and edema (Akimitsu et al, 1995;Chen et al, 1998;Huk et al, 1997;Pudupakkam et al, 1998). However, there is a dissociation between early vascular reperfusion and neutrophil infiltration from parenchymal injury and death in skeletal muscle IR (Breidahl et al, 1996;Hickey et al, 1996;Skjeldal et al, 1993Skjeldal et al, , 1994.…”

S -Nitroso Human Serum Albumin Treatment Reduces Ischemia/Reperfusion Injury in Skeletal Muscle via Nitric Oxide Release

“…1 In addition, abnormally low NO concentrations (Ͻ1 nmol/L) have been measured in microvessels in vivo during ischemia/reperfusion (I/R) by use of porphyrinic microsensors. 2 Reestablishing blood flow to ischemic tissues or organs (reperfusion) is an essential step in many surgical procedures. 3 Especially after prolonged ischemia, however, reperfusion can lead to changes in vasomotility and an increase in microvascular permeability causing tissue reperfusion edema.…”