Nitric oxide synthase (NOS) activity has been shown to increase in brain during MS withdrawal. We examined the effect of high dose MS infusion on nitric oxide (NO) end products (NO2-+NO3-) in the systemic and cerebrovascular circulation, as well as in brain tissue. Six newborn piglets received a loading dose of 100 μg/kg MS over 5 minutes, followed by a continuous i.v. infusion of 100 μg/kg/hr for 4 hours. Six control newborn piglets received equivalent volumes of D5W. Systemic arterial and sagittal sinus vein blood samples were drawn at 0, 30 minutes post-bolus, 1, 2, 3, & 4 hrs during infusion, and at 1 & 2 hrs post infusion, for determination of total NO2-+NO3- levels by the Greiss method. At the end of the experiment, the brain was removed and regional (cortex, thalamus, brain stem, cerebellum, periventricular area and choroid plexus) NO2-+NO3- levels were assessed in brain tissue homogenates (nmol/mg protein). Systemic and cerebrovascular NO2-+NO3- levels did not change in the control group over the experimental time. In contrast, systemic NO2-+NO3- levels decreased at 2 hrs during infusion (6.5±1.0 μM, p<0.01), and at 1 hr(6.4±2.0 μM, p<0.01) and 2 hrs (8.3±0.8 μM,p<0.01) post-infusion versus baseline (14.4±1.2 μM). Similarly, cerebrovascular NO2-+NO3- levels decreased significantly at 30 minutes post-bolus (9.6±0.4 μM,p<0.05), and at 2 hrs (8.2±0.8 μM, p<0.01) and 3 hrs (8.4±1.5 μM, p<0.01) during infusion versus baseline (12.8±0.4 μM). No differences in regional brain NO end products were detected between control and MS-treated animals. These data indicate that high dose MS infusion results in decreased NO production in the systemic and cerebrovascular circulation, but not in brain tissue. This response may be due to the direct effect of MS on vascular endothelial cells.
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Tumbaga, P., Beharry, K., Federico, C. et al. Attenuation of Systemic and Cerebrovascular Nitrite (NO2-) and Nitrate(NO3-) Levels With High Dose Morphine Sulfate (MS) Infusion in Newborn Piglets 354. Pediatr Res 43, 63 (1998) doi:10.1203/00006450-199804001-00375