Role of carbon monoxide in glutamate receptor-induced dilation of newborn pig pial arterioles

James S. Robinson, Alexander L. Fedinec, Charles W. Leffler
2002 American Journal of Physiology. Heart and Circulatory Physiology  
The hypothesis that glutamate dilates pial arterioles of newborn pigs through the production of carbon monoxide (CO) was addressed. Anesthesized newborn pigs were equipped with cranial windows to measure pial arteriolar responses to stimuli. Heme oxygenase (HO) inhibitors added topically inhibited dilation to glutamate and to specific glutamate receptor agonists. The initial dilation to glutamate (10 Ϫ5 M) was 22% from baseline without an inhibitor and decreased to 9% with the HO inhibitor
more » ... ium mesoporphyrin (CrMP). Inhibition of dilation upon HO inhibition was similar when specific glutamate receptor agonists were employed. RS-␣amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid caused 24% dilation from the baseline without an inhibitor, and the dilation was decreased to 1% with tin protoporphyrin (SnPP). (RS)-2-amino-3-(3-hydroxy-5-t-butylisoxazol-4-yl)propionic acid (kainate receptors) caused dilation of 18% from baseline without an inhibitor, but only 2% when tin mesoporphyrin was applied. 1-Aminocyclopropanecarboxylic acid (N-methyl-D-aspartate receptors) dilated pial arterioles 33% from baseline in control, but only to 2% in the presence of SnPP. Neither copper mesoporphyrin, which does not inhibit HO, nor light-inactivated CrMP affected the dilations. Furthermore, cerebral microvessels removed from the brain produced CO (stable isotope dilution gas chromatography-mass spectrometry), and this production was dose dependently increased by glutamate and inhibited by metal porphyrin HO inhibitors. These data suggest that dilation of newborn pig pial arterioles to glutamate and specific glutamate receptor agonists involves vascular production of CO. Additional cerebral sources of CO also could be stimulated by glutamate and contribute to the dilation. heme oxygenase; cerebral blood flow; excitatory amino acids CARBON MONOXIDE (CO) is a potent vasodilator of newborn pig cerebral arterioles in vivo (11). CO is produced from the degradation of heme to biliverdin, iron, and CO via the enzyme heme oxygenase (HO) (4). The HO-1 isoform is induced by numerous stimuli including cAMP (3) and hypoxia (7), whereas the HO-2 isoform is expressed constituitively and seems to be solely regu-
doi:10.1152/ajpheart.00911.2001 pmid:12003848 fatcat:3uyqev5gvvhqpldfaelayuakpq