Group I metabotropic glutamate receptors prevent endothelial programmed cell death independent from MAP kinase p38 activation in rat.

Activation of Group I metabotropic glutamate receptors (mGluRs) prevents neuronal programmed cell death (PCD), but the role of these receptors in the vascular endothelial cell (EC) system has not been defined. Since ECs are principal targets for ischemic free radical injury, we examined whether the mGluR system could modulate vascular PCD. Activation of the Group I mGluR system, but not antagonism, addressed two distinct pathways of PCD by preventing the destruction of genomic DNA and maintaining EC membrane asymmetry. The induction of nitric oxide (NO)-induced PCD in ECs paralleled the specific activation of the MAP kinase p38 pathway, but the vascular protection conferred by the Group I mGluR system appears to rely on more downstream cellular pathways. We provide initial evidence for Group I mGluRs to prevent NO-induced vascular injury and offer new directions for vascular disease treatment.