L-NA-Sensitive rCBF Augmentation during Vibrissal Stimulation in Type III Nitric Oxide Synthase Mutant Mice

Ayata, Cenk; Ma, Jiechao; Wang, Meng; Huang, Paul L.; Moskowitz, Michael A.

doi:10.1097/00004647-199607000-00002

Cited by 94 publications

(46 citation statements)

References 9 publications

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“…Interestingly, the whisker responses we measured over the capillary bed in barrel cortex were somewhat smaller, whereas arterial blood flow increases were larger, compared with our previous data using LDF in mice (24%) (Ayata et al, 1996). One potential explanation for this discrepancy is volume averaging by LDF.…”

Section: Figcontrasting

confidence: 86%

Laser Speckle Flowmetry for the Study of Cerebrovascular Physiology in Normal and Ischemic Mouse Cortex

Ayata

Dunn

Gürsoy‐Özdemir

et al. 2004

J Cereb Blood Flow Metab

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260

227

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Summary:Laser speckle flowmetry (LSF) is useful to assess noninvasively two-dimensional cerebral blood flow (CBF) with high temporal and spatial resolution. The authors show that LSF can image the spatiotemporal dynamics of CBF changes in mice through an intact skull. When measured by LSF, peak CBF increases during whisker stimulation closely correlated with simultaneous laser-Doppler flowmetry (LDF) measurements, and were greater within the branches of the middle cerebral artery supplying barrel cortex than within barrel cortex capillary bed itself. When LSF was used to study the response to inhaled CO 2 (5%), the flow increase was similar to the response reported using LDF. For the upper and lower limits of autoregulation, mean arterial pressure values were 110 and 40 mm Hg, respectively. They also show a linear relationship between absolute resting CBF, as determined by [ 14 C]iodoamphetamine technique, and 1/ c values obtained using LSF, and used 1/ c values to compare resting CBF between different animals. Finally, the authors studied CBF changes after distal middle cerebral artery ligation, and developed a model to investigate the spatial distribution and hemodynamics of moderate to severely ischemic cortex. In summary, LSF has distinct advantages over LDF for CBF monitoring because of high spatial resolution.

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Section: Figcontrasting

confidence: 86%

Laser Speckle Flowmetry for the Study of Cerebrovascular Physiology in Normal and Ischemic Mouse Cortex

Ayata

Dunn

Gürsoy‐Özdemir

et al. 2004

J Cereb Blood Flow Metab

Self Cite

260

227

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“…L-NNA is known to decrease the LDF response to whisker stimulation in mice (6,29). This decrease in the response was confirmed in a group of nNOS ϩ/ϩ mice after 1 h of superfusion of L-NNA (Fig.…”

Section: Resultssupporting

confidence: 58%

“…Furthermore, in nNOS ϩ/ϩ mice, the interaction of acute NOS inhibition with 20-HETE synthesis inhibition was tested with L-NNA, which was superfused for 1 h at a concentration of 1 mmol/l. This NOS inhibitor has been shown to inhibit the LDF response to whisker stimulation in mice at this concentration (6,29) and to inhibit NOS activity after 1 h of administration (24).…”

Section: Methodsmentioning

confidence: 95%

“…The homogenate was centrifuged at 4,000 g for 5 min. The supernatant was extracted twice with 3 ml of ethyl acetate after the addition of 10 ng of an internal standard, d 6 20-hydroxyeicosatetranoic acid, and the organic phase was dried under nitrogen. The metabolites of arachidonic acid were separated by high-performance liquid chromatography on a Betabasic C18 column (150 ϫ 2.1 mm, 3 m; Thermo Hypersil-Keystone, Bellefonte, PA) at a flow rate of 0.2 ml/min using an isocratic elution with a 51:9:40:0.01 mixture of acetonitrile:methanol:water:acetic acid for 30 min, followed by a step gradient to 68:13:19:01 acetonitrile:methanol:water: acetic acid and water for 15 min.…”

Section: Methodsmentioning

confidence: 99%

“…Neuronal NO synthase (nNOS) null mice (nNOS Ϫ/Ϫ ) and endothelial NOS (eNOS) null mice retain normal cerebral blood flow (CBF) responses to whisker stimulation (6,29). Further work demonstrated that NO may act in a permissive fashion in the cerebral cortex to enable vasodilation by other mediators.…”

mentioning

confidence: 99%

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Interaction of nitric oxide, 20-HETE, and EETs during functional hyperemia in whisker barrel cortex

Liu

Falck

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Nitric oxide (NO) modulates vasodilation in cerebral cortex during sensory activation. NO is known to inhibit the synthesis of 20-HETE, which has been implicated in arteriolar constriction during astrocyte activation in brain slices. We tested the hypothesis that the attenuated cerebral blood flow (CBF) response to whisker stimulation seen after NO synthase (NOS) inhibition requires 20-HETE synthesis and that the ability of an epoxyeicosatrienoic acids (EETs) antagonist to reduce the CBF response is blunted after NOS inhibition but restored with simultaneous blockade of 20-HETE synthesis. In anesthetized rats, the increase in CBF during whisker stimulation was attenuated after the blockade of neuronal NOS with 7-nitroindazole. Subsequent administration of the 20-HETE synthesis inhibitor N-hydroxy-NЈ-(4-n-butyl-2-methylphenyl)formamidine (HET0016) restored the CBF response to control levels. After the administration of 7-nitroindazole, the inhibitory effect of an EETs antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) on the CBF response was lost, whereas the simultaneous administration of 7-nitroindazole and HET0016 restored the inhibitory effect of 14,15-EEZE. The administration of HET0016 alone had only a small effect on the evoked CBF response in rats. Furthermore, in neuronal NOS ϩ/ϩ and NOS Ϫ/Ϫ mice, HET0016 administration did not increase the CBF response to whisker stimulation. In neuronal NOS ϩ/ϩ mice, HET0016 also blocked the reduction in the response seen with acute NOS inhibition. These results indicate that 20-HETE synthesis normally does not substantially restrict functional hyperemia. Increased NO production during functional activation may act dynamically to suppress 20-HETE synthesis or downstream signaling and permit EETs-dependent vasodilation. With the chronic loss of neuronal NOS in mice, other mechanisms apparently suppress 20-HETE synthesis or signaling. eicosanoids; epoxyeicosatrienoic acid; functional activation; mouse; rat; vibrissae; 20-hydroxyeicosatetraenoic acid WHEN NEURONS IN A specific brain region increase their activity, local blood flow increases in a temporally and spatially coordinated manner. The physiological mechanisms that underlie this functional coupling are complex and involve adenosine (13,31,39), nitric oxide (NO) (12, 29), arachidonic acid metabolites derived from cyclooxygenase (34) and cytochrome P-450 (CYP) epoxygenase (36) enzymes, Ca 2ϩ -activated K ϩ (K Ca ) channels, and inward-rectifier K ϩ channels (17).Although NO is required for functional hyperemia in cerebellum (50), NO may not be an essential mediator in cerebral cortex. Neuronal NO synthase (nNOS) null mice (nNOS Ϫ/Ϫ ) and endothelial NOS (eNOS) null mice retain normal cerebral blood flow (CBF) responses to whisker stimulation (6,29). Further work demonstrated that NO may act in a permissive fashion in the cerebral cortex to enable vasodilation by other mediators. Inhibition of NOS decreases basal cGMP and increases vascular tone. Restoration of vascular tone after NOS inhibition with either an...

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Astrocyte control of the cerebrovasculature

Gordon

Mulligan

MacVicar

2007

Glia

293

191

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The control of cerebral vessel diameter is of fundamental importance in maintaining healthy brain function because it is critical to match cerebral blood flow (CBF) to the metabolic demand of active neurons. Recent studies have shown that astrocytes are critical players in the regulation of cerebral blood vessel diameter and that there are several molecular pathways through which astrocytes can elicit these changes. Increased intracellular Ca 21 in astrocytes has demonstrated a dichotomy in vasomotor responses by causing the constriction as well as the dilation of neighboring blood vessels. The production of arachidonic acid (AA) in astrocytes by Ca 21 sensitive phospholipase A 2 (PLA 2 ) has been shown to be common to both constriction and dilation mechanisms. Constriction results from the conversion of AA to 20-hydroxyeicosatetraenoic acid (20-HETE) and dilation from the production of prostaglandin E 2 (PGE2) or epoxyeicosatrienoic acid (EET) and the level of nitric oxide (NO) appears to dictate which of these two pathways is recruited. In addition the activation of Ca 21 activated K 1 channels in astrocyte endfeet and the efflux of K 1 has also been suggested to modify vascular tone by hyperpolarization and relaxation of smooth muscle cells (SMCs). The wide range of putative pathways indicates that more work is needed to clarify the contributions of astrocytes to vascular dynamics under different cellular conditions. Nonetheless it is clear that astrocytes are important albeit complicated regulators of CBF. V V C 2007 Wiley-Liss, Inc.

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L-NA-Sensitive rCBF Augmentation during Vibrissal Stimulation in Type III Nitric Oxide Synthase Mutant Mice

Cited by 94 publications

References 9 publications

Laser Speckle Flowmetry for the Study of Cerebrovascular Physiology in Normal and Ischemic Mouse Cortex

Laser Speckle Flowmetry for the Study of Cerebrovascular Physiology in Normal and Ischemic Mouse Cortex

Interaction of nitric oxide, 20-HETE, and EETs during functional hyperemia in whisker barrel cortex

Astrocyte control of the cerebrovasculature

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