Apparent association of MK-801-sensitive ion channels with L-S-nitrosocysteine recognition sites in the hindlimb vasculature of the rat

This study demonstrates that the decreases in hindquarter vascular resistan ce produced by the putative endothelium-derived S-nitrosothiol, L-S-nitroso cysteine, in urethane-anesthetized rats, were attenuated by a lower dose of the N-methyl-D-aspartate (NMDA) receptor ion-channel blocker, dizocilpine (MK-801, 200 mug/kg, i.v.), whereas they were augmented by a higher dose of dizocilpine (500 mug/kg, i.v.). In contrast, L-S-nitrosocysteine-induced d ecreases in mesenteric vascular resistance were not affected by either dose of dizocilpine. The vasodilator actions of L-S-nitrosocysteine in these be ds were not affected by the competitive NMDA receptor antagonist, 2-amino-5 -phosphonovaleric acid (2-AP5). The vasodilator actions of the nitric oxide (NO) donor, (Z)-1-\N-methyl-N-[6(N- methylammoniohexyl)amino] \ diazen-1-i um-1,2-diolate (MAHMA NONOate), in these beds were not affected by dizocilp ine or by 2-AP5. These findings suggest that L-S-nitrosocysteine recognitio n sites in hindquarter but not mesenteric beds may be associated with dizoc ilpine-sensitive ion-channels similar to those in NMDA receptors. (C) 2000 Elsevier Science B.V. All rights reserved.