Effects of N-ω-Nitro-L-Arginine methyl ester on the cerebral circulation of newborn piglets quantified In Vivo by near-infrared spectroscopy

Abstract

The effects of N-ω-nitro-L-arginine methyl ester (L-NAME) on basal cerebral vascular tone, the vasodilatory effects of acetylcholine (ACh), and the cerebrovascular response to alterations in arterial carbon dioxide tension (CBVR) were investigated using near-infrared spectroscopy. Seven newborn piglets were anesthetized and mechanically ventilated; mean arterial blood pressure (MAP) was monitored and near-infrared spectroscopy used to measure changes in total cerebral Hb concentration. At the beginning of the experiment, CBVR was measured and then 10, 20, 30, and 100 mg·kg-1 L-NAME were administered sequentially; ACh (1, 2, 3, and 5 Mg) was given before and after each injection of L-NAME. At the end of this sequence, CBVR was measured again and finally sodium nitroprusside (1.5 mg·kg-1) was administered. Ten and 20 mg·kg-1 L-NAME caused a significant decrease in total cerebral Hb concentration of -0.59 (-3.21 to -0.02) and -1.46 (-6.50 to -0.15) fimol-L-1 (median and range), respectively (Wilcoxon p < 0.05), but subsequent injections did not. Ten, 20, and 100 mg·kg-1 L-NAME caused an increase in MAP (Wilcoxon p < 0.05). ACh caused an increase in total cerebral Hb concentration and a decrease in MAP that was impaired but not abolished by L-NAME (ANOVA p < 0.05). CBVR was not affected by L-NAME. Sodium nitroprusside caused a reduction in mean (SD) MAP of 4.7 (1.6) kPa, and a slower rise in [tHb] of 13.44 (2.03) μmol·L-1. Postmortem examination of three animals revealed NADPH-diaphorasc staining in neurons, cerebral blood vessels, carotid artery, and jugular vein. These results demonstrate that nitric oxide modulates basal vasodilation and part of the vasodilatory action of ACh in the newborn piglet brain, but that these effects are quantitatively small. Nitric oxide was not shown to be an important participant in CBVR. This is consistent with the suggestion that the mechanism mediated by nitric oxide may coordinate perfusion rather than control bulk flow in the developing brain. © 1993 International Pediatric Research Foundation, Inc.