ROLE OF EXCITATORY AMINO-ACIDS IN REGULATION OF RAT PIAL MICROVASCULATURE

Recently, attention has been drawn to the possibility that excitatory amino acids (EAAs) may play an important role in the pathogenesis of hypoxic-ischemic neuronal injury. Exaggerated release of EAAs and excessive stimulation of N-methyl-D-aspartate (NMDA) receptors and other EAA receptors have been suggested to contribute to neuronal death in ischemia and anoxia. A number of in vitro and in vivo experimental studies have shown that EAA-receptor antagonists exert a protective effect on the brain after cerebral ischemia. Because neurons are in close apposition to small intracerebral vessels, synaptically released EAAs might also regulate small blood vessel function. With the use of quantitative television microscopic observations, in vivo studies were undertaken on pial arterioles of rats. Perivascular administration of cumulative doses (10(-7)-10(-2) M) of L-glycine, L-glutamate, L-aspartate, and NMDA on the pial microvessels resulted in concentration-dependent constriction of pial arterioles (5-30% decreases in diameter) and cerebrovasospasm; the relative order of potency was aspartate > NMDA > glycine > glutamate. High concentrations of EAAs often resulted in rupture of postcapillary venules. No amine or opiate antagonist or cyclooxygenase inhibitor prevented or attenuated the effects of these putative EAAs. EAA-induced constriction and spasm of pial arterioles as well as rupture of venules could, however, be blocked by the noncompetitive NMDA-receptor antagonist MK-801 and by Mg2+. MK-801 also produced a concentration-dependent relaxation on normal pial arterioles. These results are compatible with the idea that a specific NMDA-receptor complex (RC) exists in rat cortical microvessels, which subserves vasoconstriction. The data could be used to suggest an important role for EAAs and, particularly, for the NMDA-RC in regulation of pial microcirculation and modulation of hypoxic-ischemic events in the rat brain.