Dilator effects of amino acid neurotransmitters on piglet pial arterioles.
We examined the effects of topically applied amino acids (glutamate, aspartate, glycine, and taurine) and a synthetic glutamate analogue [N-methyl-D-aspartate (NMDA)] on pial arteriolar tone and cortical surface cerebrospinal fluid (CSF) dilator prostanoid concentrations in anesthetized newborn pigs. We also determined whether prolonged contact of pial arterioles with glutamate (10(-3) M) and aspartate (10(-3) M) would alter arteriolar responses to exogenous isoproterenol or norepinephrine. Vascular responses were determined using the closed cranial window technique and intravital microscopy. Concentrations of prostaglandin E2 and 6-ketoprostaglandin F1 alpha in CSF under the cranial window were determined using radioimmunoassay. At the highest dose tested (10(-3) M), NMDA dilated arterioles by 30 +/- 4% (n = 8), glutamate by 21 +/- 5% (n = 6), aspartate by 28 +/- 10% (n = 5), and taurine by 21 +/- 2% (n = 7). Glycine application did not change pial arteriolar diameter significantly (n = 8). The amino acids tested (NMDA and glutamate) did not increase CSF levels of dilator prostagnoids, and intravenous indomethacin trihydrate did not change vascular responsiveness to NMDA. Furthermore, dilator responsiveness to isoproterenol and constrictor responsiveness to norepinephrine were not affected significantly after 30 min of topical application of glutamate and aspartate to the pial surface (n = 4). We conclude that these amino acids are potent dilators of the neonatal cerebral circulation. The mechanism of dilation in the cases of NMDA and glutamate does not appear to involve dilator prostanoids. Furthermore, prolonged contact with excitatory amino acids under these conditions does not alter subsequent cerebrovascular responsiveness.
Busija
D W
DW
Department of Physiology, University of Tennessee, Memphis 38163.
Leffler
C W
CW
D015121:6-Ketoprostaglandin F1 alpha / Q000134:cerebrospinal fluid; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000502:physiology*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001224:Aspartic Acid / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D015232:Dinoprostone / Q000134:cerebrospinal fluid; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D012016:Reference Values; D013552:Swine; D013654:Taurine / Q000494:pharmacology
D000596:Amino Acids; D005971:Glutamates; D018377:Neurotransmitter Agents; D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; D015121:6-Ketoprostaglandin F1 alpha; D016202:N-Methylaspartate; D015232:Dinoprostone; D007545:Isoproterenol; D005998:Glycine; D009638:Norepinephrine