A role for L-glutamate ionotropic receptors in the development of rat neurogenic pulmonary edema

The present study was undertaken to evaluate possible roles of L-glutamate ionotropic receptors in neurogenic pulmonary edema. Perfusion of L-glutamate into the fourth ventricles of rats increased nitric oxide (NO) signals in the efflux solution concentration-dependently, significantly reducing both the occurrence and severity of neurogenic pulmonary edema. This effect was completely reversed by prior intracisternal injection of an NO synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), or an N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine maleate (MK-801), and partially by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a 2-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid (AMPA)/kainic acid receptor antagonist. Administration of MK-801 or CNQX alone, without L-glutamate, almost completely prevented neurogenic pulmonary edema development. These results suggest that endogenous L-glutamate may facilitate underlining disease process, whereas L-glutamate exogenously applied into the fourth ventricle may have an inhibitory action via release of NO, through ionotropic receptors. (C) 2004 Elsevier B.V. All rights reserved.