Effects of Hypoxia and Reoxygenation on Nitric Oxide Production and Cerebral Blood Flow in Developing Rat Striatum

Abstract

We investigated the role of nitric oxide (NO) in the regulation of regional cerebral blood flow (rCBF) during hypoxia and reoxygenation in developing rat striatum. The subjects were urethane-anesthetized 7- and 14-d-old rats. After 120 min of baseline measurements, the rats received an i.p. injection of either saline (as a control) or an NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) 30 min before hypoxia. Then they were subjected to a 60-min hypoxia in 8% O2, followed by a 60-min recovery in 21% O2. rCBF and NO concentration in the striatum were measured by laser Doppler flowmetry and an NO electrode throughout the experimental period. In the controls, rCBF decreased to 93 +/- 3% of baseline during hypoxia and increased to 124 +/- 3% of baseline during reoxygenation in 7-d-old rats (n = 13), whereas rCBF increased during both hypoxia and reoxygenation in 14-d-old rats to 125 +/- 6% and 168 +/- 6% of baseline, respectively (n = 17). L-NAME attenuated the hyperemic response to hypoxia/reoxygenation in both ages (n = 11, in each age). Striatal NO production increased during hypoxia and reoxygenation in both ages, but the increase was significantly less in 7-d-old than in 14-d-old rats. The NO increase was associated with the increase in rCBF, and both were attenuated by L-NAME. We speculate that NO release during hypoxia/reoxygenation modulates rCBF. The immature young rat brain may have less capacity to activate NO production than the more developed brain.

Effects of Hypoxia and Reoxygenation with 21% and 100%-Oxygen on Cerebral Nitric Oxide Concentration and Microcirculation in Newborn Piglets

“…The use of inhibitors of NO synthase may provide indirect evidence for the involvement of NO in the regulation of CBF [20,34]. The suggestion by several authors that hypoxic vasodilation in the brain is induced by increased NO concentration [20,34] is not supported by the present study. Hypoxic hypoxia itself may interfere with CBF and lead to cerebral hyperemia [34,38].…”

“…Administration of the NO donor sodium nitroprussid may increase CBF in ischemic regions of the brain [37]. The use of inhibitors of NO synthase may provide indirect evidence for the involvement of NO in the regulation of CBF [20,34]. The suggestion by several authors that hypoxic vasodilation in the brain is induced by increased NO concentration [20,34] is not supported by the present study.…”

“…The small size (diameter 200 Ìm), the fast response time of ! 5 s (90% response) and the fast recovery time following exposure to NO makes the NO meter a valuable tool for measuring NO directly [20,21].…”

Physiologically Relevant Measurements of Nitric Oxide in Cardiovascular Research Using Electrochemical Microsensors

“…Insertion of microelectrodes in the cortex or other regions of the brain has also allowed in vivo measurement of changes in NO concentration during ischaemia or hypoxia [107,108,109]. In a model of focal ischaemia in cats, occlusion of the middle cerebral artery reduced cerebral blood flow, and NO concentration increased simultaneously in the regions of the brain where depolarization takes place during ischaemia, and then, similar to the situation in limb ischaemia, decreases even below baseline levels over the next 60 min [107].…”

Greater Resistance and Lower Contribution of Free Radicals to Hypoxic Neurotoxicity in Immature Rat Brain Compared to Adult Brain as Revealed by Dynamic Changes in Glucose Metabolism

“…As the mechanism of progression of neurotoxicity in ischemia/hypoxia, the excitotoxicity of N-methyl-D-aspartate (NMDA) based on glutamate release induced by energy insufficiency and the production of free radicals following reoxygenation have been proposed [McCord, 1985;Braughler and Hall, 1989;Hall and Braughler, 1989]. However, there is not yet a consensus on the maturational difference in vulnerability to NMDA excitotoxicity [Hattori et al, 1989;Hagberg et al, 1994;Berger et al, 1997] or free radicals [Hamada et al, 1994;Schreiber et al, 1995;Keelan et al, 1996;Ioroi et al, 1998;Nakai et al, 2000] in ischemic/hypoxic brain injury. There have been few studies that compared the neuroprotective effects of NMDA antagonists or free radical scavengers between immature and adult animals.…”