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Vol. 281, Issue 1, 448-453, 1997

L-Glutamine Inhibits Nitric Oxide Synthesis in Bovine Venular Endothelial Cells1

Cynthia J. Meininger and Guoyao Wu

Departments of Medical Physiology (C.J.M., G.W.) and Animal Science (G.W.) Texas A&M University, College Station, Texas

This study was conducted to test the hypothesis that L-glutamine has differential effects on nitric oxide (NO) synthesis from L-arginine in bovine venular endothelial cells (EC) stimulated by A23187 (a Ca++ ionophore) and receptor-mediated vasodilators (bradykinin and substance P). EC were cultured at 37°C for 24 h in the presence of 0.4 mM L-arginine and 0.0 to 2.0 mM L-glutamine with or without 1 µM A23187, 1 µM bradykinin or 10 µM substance P. The release of nitrite and nitrate by EC was used as an indicator of NO synthesis. A23187, bradykinin or substance P increased NO synthesis from L-arginine by EC in the presence or absence of L-glutamine. The addition of L-glutamine (0.5 and 2 mM) markedly increased intracellular concentrations of L-glutamine, L-glutamate and L-aspartate and decreased NO synthesis by EC in a concentration-dependent manner in the presence or absence of A23187, bradykinin or substance P. L-Glutamine had no effect on L-arginine uptake by EC or on intracellular L-arginine concentration. Neither L-glutamine nor its glutaminase metabolites (ammonia, L-glutamate and L-aspartate) had any effect on endothelial NO synthase activity. Taken together, these results suggest that the inhibition by L-glutamine of NO synthesis from L-arginine is unlikely to result from an effect of L-glutamine on L-arginine transport or NO synthase activity. Although the mechanism involved remains unknown, regulation of the arginine-NO pathway by L-glutamine may have pharmacologic and therapeutic implications in such conditions as inflammation and septic shock by inhibiting NO generation from L-arginine in endothelial cells.


Copyright © by The American Society for Pharmacology and Experimental Therapeutics



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