ROLE OF ENDOTHELIAL NITRIC-OXIDE SYNTHASE IN HYPOXIA-INDUCED PIAL ARTERY DILATION

Nitric oxide (NO) contributes to hypoxia-induced pial artery dilation, at least in part, through the formation of cGMP and the subsequent re lease of methionine enkephalin and leucine enkephalin in the newborn p ig. In separate studies, these opioids also were observed to elicit NO -dependent pial artery dilation, whereas light/dye endothelial injury reduced hypoxic pial dilation. The current study was designed to inves tigate the role of the endothelial isoform of NO synthase in hypoxic p ial dilation, associated opioid release, and opioid dilation in piglet s equipped with a closed cranial window. N-iminoethyl-L-ornithine (L-N IO) (10(-6) mol/L), an antagonist that may have greater endothelial NO synthase inhibitory selectivity, had no effect on dilation elicited b y hypoxia (Po-2 approximate to 35 mm Hg) (24 +/- 2 versus 24 +/- 2% in the absence and presence of L-NIO, respectively, n = 8). Hypoxic dila tion was accompanied by increased CSF cGMP, which also was unchanged i n the presence of L-NIO (394 +/- 19 and 776 +/- 63 versus 323 +/- 13 a nd 739 +/- 25 fmol/mL for control and hypoxia in the absence and prese nce of L-NIO, respectively, n = 6). Additionally, hypoxic pial dilatio n was associated with increased CSF methionine enkephalin, which also was unchanged in the presence of L-NIO (992 +/- 73 and 2469 +/- 197 ve rsus 984 +/- 18 and 2275 +/- 185 pg/mL, respectively, n = 6). In contr ast, methionine enkephalin-induced dilation was blocked by L-MO (6 +/- 1, 10 +/- 1, and 16 +/- 1 versus 1 +/- 1, 1 +/- 1, and 2 +/- 1% for 1 0(-10), 10(-8), 10(-6) mol/L methionine enkephalin, respectively, befo re and after L-NIO, n = 8). Substance P-induced pial dilation was blun ted by L-MO, whereas responses to sodium nitroprusside and N-methyl-D- aspartate were unchanged. These data indicate that endothelial NO synt hase contributes to opioid-induced pial artery dilation but not hypoxi a-induced dilation. Additionally, these data suggest that neuronally d erived NO contributes to hypoxic pial dilation.