Nitric oxide mediates vasodilatation in response to activation of N-methyl-D-aspartate receptors in brain.

Faraci, Frank M.; Breese, Keith

doi:10.1161/01.res.72.2.476

Cited by 303 publications

(225 citation statements)

References 32 publications

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“…Cerebral blood flow reductions of this magnitude compare well with other studies using nNOS inhibition (Dirnagl et al, 1993). Neuronal NO synthesis may be associated with NMDAR activation (Faraci and Breese, 1993;Pelligrino et al, 1996;Bhardwaj et al, 2000). The NMDAR has been linked physically to neuronal NOS (nNOS) through specific protein structures (PSD-95) at the postsynaptic excitatory synapse, facilitating nNOS activation by NMDAR mediated calcium influx (Brenman et al, 1996;Sattler et al, 1999).…”

Section: The Neurovascular Coupling: Linearity Versus Nonlinearitysupporting

confidence: 79%

Nonlinear Neurovascular Coupling in Rat Sensory Cortex by Activation of Transcallosal Fibers

Hoffmeyer

Enager

Thomsen

et al. 2006

J Cereb Blood Flow Metab

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Functional neuroimaging and normal brain function rely on the robust coupling between neural activity and cerebral blood flow (CBF), that is neurovascular coupling. We examined neurovascular coupling in rat sensory cortex in response to direct stimulation of transcallosal pathways, which allows examination of brain regions inaccessible to peripheral stimulation techniques. Using laserDoppler flowmetry to record CBF and electrophysiologic recordings of local field potentials (LFPs), we show an exponential relation between CBF responses and summed LFP amplitudes. Hemodynamic responses were dependent on glutamate receptor activation. CNQX, an AMPA receptor blocker, strongly attenuated evoked CBF responses and LFP amplitudes at all stimulation frequencies. In comparison, N-methyl D-aspartate (NMDA) receptor blockade by MK801 attenuated CBF responses at high ( > 7 Hz) but not low ( < 7 Hz) stimulation frequencies, without affecting evoked LFP amplitudes. This shows the limitation of using LFP amplitudes as indicators of synaptic activity. 7-Nitroindazole, a neuronal nitric oxide synthase inhibitor, and indomethacin, a nonspecific cyclooxygenase inhibitor, attenuated the hemodynamic responses by 50%61% and 48%61%, respectively, without affecting LFP amplitudes. The data suggest that preserved activity of both AMPA and NMDA receptors is necessary for the full CBF response evoked by stimulation of rodent interhemispheric connections. AMPA receptor activation gives rise to a measurable LFP, but NMDA receptor activation does not. The lack of a measurable LFP from neural processes that contribute importantly to CBF may explain some of the difficulties in transforming extracellular current or voltage measurements to a hemodynamic response.

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Section: The Neurovascular Coupling: Linearity Versus Nonlinearitysupporting

confidence: 79%

Nonlinear Neurovascular Coupling in Rat Sensory Cortex by Activation of Transcallosal Fibers

Hoffmeyer

Enager

Thomsen

et al. 2006

J Cereb Blood Flow Metab

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“…Faraci and Breese (1993) found that activation of the receptors for NMDA produces dilatation of the cerebral microcirculation that is mediated by NO. This and other findings suggest that NO generated in response to activation of the NMDA receptors in vivo is neuronally derived.…”

Section: Nitric Oxidementioning

confidence: 99%

Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

Gjedde

Johannsen

Cold

et al. 2005

J Cereb Blood Flow Metab

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The reactions of cerebral metabolism to imposed changes of cerebral blood flow (CBF) are poorly understood. A common explanation of the mismatched CBF and oxygen consumption (CMR O 2 ) during neuronal excitation holds that blood flow rises more than oxygen consumption to compensate for an absent oxygen reserve in brain mitochondria. The claim conversely implies that oxygen consumption must decline when blood flow declines. As the prevailing rate of reaction of oxygen with cytochrome c oxidase is linked to the tension of oxygen, the claim fails to explain how oxygen consumption is maintained during moderate reductions of CBF imposed by hyperventilation (hypocapnia) or cyclooxygenase (COX) inhibition. To resolve this contradiction, we extended the previously published oxygen delivery model with a term allowing for the adjustment of the affinity of cytochrome c oxidase to a prevailing oxygen tension. The extended model predicted constant oxygen consumption at moderately reduced blood flow. We determined the change of affinity of cytochrome c oxidase in the extended model by measuring CBF in seven, and CMR O 2 in five, young healthy volunteers before and during COX inhbition with indomethacin. The average CBF declined 35%, while neither regional nor average CMR O 2 changed significantly. The adjustment of cytochrome c oxidase affinity to the declining oxygen delivery could be ascribed to a hypothetical factor with several properties in common with nitric oxide.

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“…Activation of these receptors has been shown to stimulate the synthesis/release of neuronal nitric oxide (Agullo and Garcia, 1992;Garthwaite et al, 1989a;Garthwaite et al, 1989b;Murphy et al, 1993). We (Sun et al, 2002) and others (Busija and Leffler, 1989;Faraci and Breese, 1993;Faraci and Brian, 1995) have shown that application of NMDA and kainate dilates cerebral arterioles via the synthesis/release of nitric oxide (Faraci and Breese, 1993;, presumably by activation of nNOS (Faraci and Brian, 1995;Sun et al, 2002). Thus, it appears that the use of NMDA and kainate to evaluate nNOS-dependent dilatation of cerebral arterioles is appropriate.…”

Section: Consideration Of Methodsmentioning

confidence: 87%

“…Activation of nNOS has been suggested to be responsible for, or at least contribute to, the coupling of local cerebral metabolism to changes in cerebral blood flow (Busija and Leffler, 1989;Faraci and Breese, 1993;Fergus and Lee, 1997). Thus, the activation of nNOS represents a major network for the control of cerebral arteriolar diameter and cerebral blood flow.…”

Section: Consideration Of Previous Studiesmentioning

confidence: 99%

“…Dilatation of cerebral arterioles in response to NMDA and kainate also can be attenuated by inhibition of nNOS (7-nitroindozole) (Faraci and Brian, 1995;Sun et al, 2002). Activation of nNOS has been suggested to represent a mechanism responsible for the coupling of local cerebral metabolism to changes in cerebral blood flow (Busija and Leffler, 1989;Faraci and Breese, 1993;Fergus and Lee, 1997). Thus, the release of nitric oxide via activation of nNOS represents a major pathway for the control of cerebral arteriolar diameter and cerebral blood flow.…”

Section: Introductionmentioning

confidence: 99%

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nNOS-dependent reactivity of cerebral arterioles in Type 1 diabetes

et al. 2007

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Our goals were to determine whether Type 1 diabetes (T1D) alters neuronal nitric oxide synthase (nNOS) dependent reactivity of cerebral arterioles and to identify a potential role for oxidative stress in T1D-induced impairment in nNOS-dependent responses of cerebral arterioles. Rats were injected with vehicle (sodium citrate buffer) or streptozotocin (50 mg/kg IP) to induce T1D. Two to three months later, we measured functional responses of cerebral arterioles to nNOS-dependent (NMDA and kainate) and -independent (nitroglycerin) agonists in nondiabetic and diabetic rats before and during inhibition of oxidative stress using tempol (100 μM). In addition, we measured superoxide anion production under basal conditions, during stimulation with NMDA and kainate, and during treatment with tempol. We found that nNOS-dependent, but not -independent, vasodilatation was impaired in diabetic compared to nondiabetic rats. In addition, treatment of the cerebral microcirculation with tempol restored impaired nNOS-dependent vasodilatation in diabetic rats towards that observed in nondiabetic rats. Further, the production of superoxide anion (lucigenin chemiluminescence) was increased in parietal cortical tissue of diabetic rats under basal conditions. Application of NMDA and kainate did not increase superoxide anion production in nondiabetic or diabetic rats. However, tempol decreased basal production of superoxide anion in diabetic rats. Our findings suggest that T1D impairs nNOS dependent dilatation of cerebral arterioles by a mechanism that appears to be related to the formation of superoxide anion.

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Nitric oxide mediates vasodilatation in response to activation of N-methyl-D-aspartate receptors in brain.

Cited by 303 publications

References 32 publications

Nonlinear Neurovascular Coupling in Rat Sensory Cortex by Activation of Transcallosal Fibers

Nonlinear Neurovascular Coupling in Rat Sensory Cortex by Activation of Transcallosal Fibers

Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

nNOS-dependent reactivity of cerebral arterioles in Type 1 diabetes

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